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Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis

Hui Xue, Dike Tao, Yuteng Weng, Qiqi Fan, Shuang Zhou, Ruilin Zhang, Han Zhang, Rui Yue, Xiaogang Wang, Zuolin Wang, Yao Sun

《医学前沿（英文）》 2019年第13卷第5期页码 575-589 doi: 10.1007/s11684-019-0693-9

摘要： Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.

关键词： fracture extracellular matrix dentin matrix protein 1 proteoglycan cartilage

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immune mapped protein 1 (NcIMP1) is a novel vaccine candidate against neosporosis

Xia CUI,Daoyu YANG,Tao LEI,Hui WANG,Pan HAO,Qun LIU

《农业科学与工程前沿（英文）》 2015年第2卷第1期页码 66-72 doi: 10.15302/J-FASE-2015047

摘要： The immune mapped protein 1 (NcIMP1) was identified as a membrane protein, and a previous study indicated that NcIMP1 could be a promising vaccine candidate against neosporosis. In this study, the immune response and protection efficacy of NcIMP1 were evaluated. The coding sequence of NcIMP1 was inserted into the eukaryotic expression vector pcDNA 3.1(+), resulting in the recombination plasmid pcDNA-IMP1, which was used for the intramuscular immunization of BALB/c mice. After immunization, the immune response was evaluated using a lymphoproliferative assay and cytokine and antibody measurements. Quantification of the cerebral parasite burden of mice challenged with 2 × 10 was performed 14 days after the last immunization. The results showed that the mice immunized with pcDNA-IMP1 developed a high level of specific antibody responses against recombinant NcIMP1, with a mixed IgG1/IgG2a response and a predominance of IgG2a production. The cellular immune response was associated with the production of IFN-γ, IL-2, IL-4 and IL-10 cytokines. The experiment was terminated 30 days p.i., and the cerebral parasite burden in each mouse was assessed by quantitative PCR. The parasite burden was significantly reduced in the pcDNA-IMP1-vaccinated mice. These data suggest that IMP1 is a promising vaccine candidate against neosporosis.

关键词： Neospora caninum immune mapped protein 1 (IMP1) vaccine candidate BALB/c mice

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Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependentfibrinolysis and matrix invasion in acute promyelocytic leukemia

null

《医学前沿（英文）》 2017年第11卷第3期页码 410-422 doi: 10.1007/s11684-017-0527-6

摘要：

Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5′-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29±0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

关键词： annexin A2-S100A10 heterotetramer PML/RARα fusion protein plasmin cell invasion acute promyelocytic leukemia

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Influence of retinoic acid on TBX1 expression in myocardial cells induced by Shh and Fgf8

Miao LIU, Xiaoyan WU, Jiawei XU, Runming JIN

《医学前沿（英文）》 2009年第3卷第1期页码 61-66 doi: 10.1007/s11684-009-0007-8

摘要： The aim of this study was to explore the regulatory mechanism of retinoic acid (RA) on the TBX1 gene expression in myocardial cells. Ventricular cardiocytes were isolated from neonatal rats and cultured, and then treated with different concentrations of retinoic acid. The expression of Shh and Fgf8 at mRNA and protein levels in neonatal rat myocardial cells were measured by using RT-PCR and Western blot technique, respectively. There was basal expression of Shh and Fgf8 in the control group. When treated with 3×10 mol/L RA, we observed that the expression of Shh mRNA and protein in neonatal rat myocardial cells were up-regulated by 1.51 ( <0.05) and 1.10 times ( <0.05), respectively. In comparison with the control group, under the concentration of 5×10 mol/L RA, they were up-regulated by 2.21 ( <0.05) and 2.38 times ( <0.05) individually. Meanwhile, we could detect that the expression of Fgf8 mRNA and protein were up-regulated by 2.50 times ( <0.05) and 80% ( <0.05) separately compared with the control group after stimulation of 3×10 mol/L RA, and they were up-regulated by 3.48 ( <0.05) and 2.04 times ( <0.05) individually after stimulation of 5×10 mol/L RA. The results indicated that RA could induce the expression of Shh and Fgf8 in neonatal rat myocardial cells. At the same time, it has shown that Shh and Fgf8 were involved in the regulation process of RA on TBX1 expression.

关键词： retinoic acid Tbx1 protein Shh protein Fgf8 protein

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PROTECTIVE ROLES OF D1 PROTEIN TURNOVER AND THE XANTHOPHYLL CYCLE IN TOMATO (

Tao LU, Jiazhi LU, Mingfang QI, Zhouping SUN, Yufeng LIU, Tianlai LI

《农业科学与工程前沿（英文）》页码 262-279 doi: 10.15302/J-FASE-2021383

摘要： D1 protein turnover and the xanthophyll cycle (XC) are important photoprotective mechanisms in plants that operate under adverse conditions. Here, streptomycin sulfate (SM) and dithiothreitol (DTT) were used in tomato plants as inhibitors of D1 protein turnover and XC to elucidate their photoprotective impacts under sub-high temperature and high light conditions (HH, 35°C, 1000 µmol·m ·s ). SM and DTT treatments significantly reduced the net photosynthetic rate, apparent quantum efficiency, maximum photochemical efficiency, and potential activity of photosystem II, leading to photoinhibition and a decline in plant biomass under HH. The increase in reactive oxygen species levels resulted in thylakoid membrane lipid peroxidation. In addition, there were increased non-photochemical quenching and decreased chlorophyll pigments in SM and DTT application, causing an inhibition of D1 protein production at both transcriptional and translational levels. Overall, inhibition of D1 turnover caused greater photoinhibition than XC inhibition. Additionally, the recovery levels of most photosynthesis indicators in DTT-treated plants were higher than in SM-treated plants. These findings support the view that D1 turnover has a more important role than XC in photoprotection in tomato under HH conditions.

关键词： D1 turnover photoinhibition photoprotection photosynthesis tomato xanthophyll cycle

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PROTECTIVE ROLES OF D1 PROTEIN TURNOVER AND THE XANTHOPHYLL CYCLE IN TOMATO (SOLANUM LYCOPERSICUM) UNDER

《农业科学与工程前沿（英文）》 2021年第8卷第2期

摘要：

D1 protein turnover and the xanthophyll cycle (XC) are important photoprotective mechanisms in plants that operate under adverse conditions. Here, streptomycin sulfate (SM) and dithiothreitol (DTT) were used in tomato plants as inhibitors of D1 protein turnover and XC to elucidate their photoprotective impacts under sub-high temperature and high light conditions (HH, 35°C, 1000 µmol·m^-²·s^-¹). SM and DTT treatments significantly reduced the net photosynthetic rate, apparent quantum efficiency, maximum photochemical efficiency, and potential activity of photosystem II, leading to photoinhibition and a decline in plant biomass under HH. The increase in reactive oxygen species levels resulted in thylakoid membrane lipid peroxidation. In addition, there were increased non-photochemical quenching and decreased chlorophyll pigments in SM and DTT application, causing an inhibition of D1 protein production at both transcriptional and translational levels. Overall, inhibition of D1 turnover caused greater photoinhibition than XC inhibition. Additionally, the recovery levels of most photosynthesis indicators in DTT-treated plants were higher than in SM-treated plants. These findings support the view that D1 turnover has a more important role than XC in photoprotection in tomato under HH conditions.

关键词： D1 turnover / photoinhibition / photoprotection / photosynthesis / tomato / xanthophyll cycle

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基于随机矩阵理论的子空间加权改良算法 Research Articles

高雨濛1,李姜辉2,柏业超1,王琼1,张兴敢1

《信息与电子工程前沿（英文）》 2020年第21卷第9期页码 1302-1307 doi: 10.1631/FITEE.1900463

摘要：在低信噪比及信号相关情况下，加权子空间拟合（WSF）算法的性能优于多信号分类（MUSIC）算法。本文使用随机矩阵理论（RMT）改善加权子空间拟合。随机矩阵理论研究随机矩阵维数以同速率增加时，矩阵特征值和特征向量的渐近规律。加权子空间拟合中，运用近似一阶扰动计算样本协方差矩阵特征向量的统计特性。利用随机矩阵理论中关于样本协方差矩阵信号子空间向真实信号投影的范数的渐进结果，获得加权子空间拟合计算方法。仿真结果表明，在低快拍数及低信噪比情况下，本文所提方法具有优越性。

关键词：波达方向；信号子空间；随机矩阵理论

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以Matrix-3000为例研究面向裸金属加速器的异构多线程编程模型 Research Article

方建滨1,张鹏1,黄春1,唐滔1,卢凯1,王睿伯1,王峥2

《信息与电子工程前沿（英文）》 2023年第24卷第4期页码 509-520 doi: 10.1631/FITEE.2200359

摘要：以Matrix-3000为代表的新型处理器具有复杂的内存层次结构和处理器组织，是为下一代E级超级计算机设计的高性能处理器。本文分享了我们为Matrix-3000开发的并行编程模型及其支持编译器和库的经验。为了帮助软件开发，我们从头开始开发了一个针对Matrix-3000的软件栈，包括一个低层次的编程接口和一个高层次的OpenCL编译器。该低层次编程模型为使用Matrix-3000的裸金属加速器提供了原生编程支持，而高层次模型允许程序员使用OpenCL并行编程标准。

关键词：异构计算；并行编程模型；可编程性；编译器；运行时系统

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Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

《医学前沿（英文）》 2009年第3卷第3期页码 309-315 doi: 10.1007/s11684-009-0043-4

摘要： Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 0.008±0.002 of controls, =0.009; in liver: 0.165±0.006 0.017±0.006 of controls, =0.004; in small intestine: 0.215±0.009 0.016±0.002 of controls, =0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 0.003±0.001 of controls, =0.008; in small intestine: 0.006±0.001 0.003±0.001 of controls, =0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

关键词： graft vs host disease proteinase-activated receptor murine model hematopoietic stem cell transplantation

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城市轨道交通建设管理中WBS矩阵技术研究

谢磊,陈群,虞华

《中国工程科学》 2010年第12卷第1期页码 102-107

摘要：

为提高城市轨道交通的建设管理水平，引用了WBS（work breakdown structure，工作分解结构）理念，通过对城市轨道交通建设活动的水平分解和其技术系统的垂直分解，形成了比WBS树状图更完整、更有价值的WBS矩阵；在阐明界面和WBS矩阵概念的基础上，分析如何运用WBS矩阵以提高城市轨道交通建设管理的界面管理水平；采用对比分析法对WBS矩阵的组成、结构系统、原则以及WBS矩阵实施效率的影响因素进行了具体的分析。

关键词：城市轨道交通 WBS矩阵界面界面管理

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一种基于矩阵的有限状态机静态分析方法 Research Article

邓鹤1,闫永义1,陈增强2

《信息与电子工程前沿（英文）》 2022年第23卷第8期页码 1239-1246 doi: 10.1631/FITEE.2100561

摘要：在有限状态机研究领域，传统矩阵法首先构造状态转移矩阵，然后利用状态转移矩阵的幂来表示系统动态转移过程。这一过程是有限状态机系统分析的基石。本文提出一种基于矩阵的静态方法。该方法从拓扑结构的视角审视有限状态机，而非传统动态转移过程的视角，因此能够避免现有方法中存在的“维度爆炸”问题。基于这种静态方法，本文重新分析确定有限状态机的闭环检测与可控性问题。此外，我们提出可控等价型与最小可控等价型概念，并给出相关算法。

关键词：逻辑系统；有限值系统；矩阵的半张量积；有限状态机；矩阵方法

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proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1

《医学前沿（英文）》 2023年第17卷第3期页码 458-475 doi: 10.1007/s11684-022-0968-4

摘要： The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

关键词： LU domain-containing protein family novel human gene LY6A pituitary tumor biomarker nonsynonymous SNP GPI-anchored protein

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Identification of variants associated with sporadic thoracic aortic dissection: a case--control study

《医学前沿（英文）》 2021年第15卷第3期页码 438-447 doi: 10.1007/s11684-020-0826-1

摘要： Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10⁻⁶) after 10 000 times permutation test (P = 2.49 × 10⁻³). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.

关键词： sporadic thoracic aortic dissection exome sequencing gene COL3A1 case–control study extracellular matrix

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

《工程（英文）》 2024年第32卷第1期页码 58-69 doi: 10.1016/j.eng.2023.09.019

摘要：

Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells

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Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

null

《医学前沿（英文）》 2016年第10卷第1期页码 52-60 doi: 10.1007/s11684-016-0433-3

摘要：

Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P= 0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC-specific overall survival (HR, 2.799; 95% CI, 1.346–5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

关键词： PPM1D hepatocellular carcinoma prognosis target therapy

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标题作者时间类型操作

Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis

Hui Xue, Dike Tao, Yuteng Weng, Qiqi Fan, Shuang Zhou, Ruilin Zhang, Han Zhang, Rui Yue, Xiaogang Wang, Zuolin Wang, Yao Sun

期刊论文

immune mapped protein 1 (NcIMP1) is a novel vaccine candidate against neosporosis

Xia CUI,Daoyu YANG,Tao LEI,Hui WANG,Pan HAO,Qun LIU

期刊论文

Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependentfibrinolysis and matrix invasion in acute promyelocytic leukemia

null

期刊论文

Influence of retinoic acid on TBX1 expression in myocardial cells induced by Shh and Fgf8

Miao LIU, Xiaoyan WU, Jiawei XU, Runming JIN

期刊论文

PROTECTIVE ROLES OF D1 PROTEIN TURNOVER AND THE XANTHOPHYLL CYCLE IN TOMATO (

Tao LU, Jiazhi LU, Mingfang QI, Zhouping SUN, Yufeng LIU, Tianlai LI

期刊论文

PROTECTIVE ROLES OF D1 PROTEIN TURNOVER AND THE XANTHOPHYLL CYCLE IN TOMATO (SOLANUM LYCOPERSICUM) UNDER

期刊论文

基于随机矩阵理论的子空间加权改良算法

高雨濛1,李姜辉2,柏业超1,王琼1,张兴敢1