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11.
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα
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Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang 《Cell biochemistry and function》2016,34(8):606-612
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. 相似文献
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Mridusmita Saikia Ye Fu Mariana Pavon-Eternod Chuan He Tao Pan 《RNA (New York, N.Y.)》2010,16(7):1317-1327
The N1-methyl-Adenosine (m1A58) modification at the conserved nucleotide 58 in the TΨC loop is present in most eukaryotic tRNAs. In yeast, m1A58 modification is essential for viability because it is required for the stability of the initiator-tRNAMet. However, m1A58 modification is not required for the stability of several other tRNAs in yeast. This differential m1A58 response for different tRNA species raises the question of whether some tRNAs are hypomodified at A58 in normal cells, and how hypomodification at A58 may affect the stability and function of tRNA. Here, we apply a genomic approach to determine the presence of m1A58 hypomodified tRNAs in human cell lines and show how A58 hypomodification affects stability and involvement of tRNAs in translation. Our microarray-based method detects the presence of m1A58 hypomodified tRNA species on the basis of their permissiveness in primer extension. Among five human cell lines examined, approximately one-quarter of all tRNA species are hypomodified in varying amounts, and the pattern of the hypomodified tRNAs is quite similar. In all cases, no hypomodified initiator-tRNAMet is detected, consistent with the requirement of this modification in stabilizing this tRNA in human cells. siRNA knockdown of either subunit of the m1A58-methyltransferase results in a slow-growth phenotype, and a marked increase in the amount of m1A58 hypomodified tRNAs. Most m1A58 hypomodified tRNAs can associate with polysomes in varying extents. Our results show a distinct pattern for m1A58 hypomodification in human tRNAs, and are consistent with the notion that this modification fine tunes tRNA functions in different contexts. 相似文献
13.
Congenital diaphragmatic hernia must be seriously considered in the differential diagnosis of acute respiratory distress in neonates as well as in older infants who present with chronic progressive gastrointestinal and respiratory symptoms. An x-ray film of the chest is mandatory and is almost always diagnostic. Immediate nasogastric decompression of the stomach, with simultaneous fluid and electrolyte replacement and prompt surgical intervention offers the patient the best chance of survival. 相似文献
14.
Zhihui Feng Zhongbo Liu Xuesen Li Haiqun Jia Lijuan Sun Chuan Tian Lihong Jia Jiankang Liu 《The Journal of nutritional biochemistry》2010,21(12):1222-1231
Vitamin E has long been identified as a major lipid-soluble chain-breaking antioxidant in mammals. α-Tocopherol is a vitamin E component and the major form in the human body. We propose that, besides its direct chain-breaking antioxidant activity, α-tocopherol may exert an indirect antioxidant activity by enhancing the cell's antioxidant system as a Phase II enzyme inducer. We investigated α-tocopherol's inducing effect on Phase II enzymes and its protective effect on acrolein-induced toxicity in a human retinal pigment epithelial (RPE) cell line, ARPE-19. Acrolein, a major component of cigarette smoke and also a product of lipid peroxidation, at 75 μmol/L over 24 h, caused significant loss of ARPE-19 cell viability, increased oxidative damage, decreased antioxidant defense, inactivation of the Keap1/Nrf2 pathway, and mitochondrial dysfunction. ARPE-19 cells have been used as a model of smoking- and age-related macular degeneration. Pretreatment with α-tocopherol activated the Keap1/Nrf2 pathway by increasing Nrf2 expression and inducing its translocation to the nucleus. Consequently, the expression and/or activity of the following Phase II enzymes increased: glutamate cysteine ligase, NAD(P)H:quinone oxidoreductase 1, heme-oxygenase 1, glutathione S-transferase and superoxide dismutase; total antioxidant capacity and glutathione also increased. This antioxidant defense enhancement protected ARPE-19 cells from an acrolein-induced decrease in cell viability, lowered reactive oxygen species and protein oxidation levels, and improved mitochondrial function. These results suggest that α-tocopherol protects ARPE-19 cells from acrolein-induced cellular toxicity, not only as a chain-breaking antioxidant, but also as a Phase II enzyme inducer. 相似文献
15.
Chuan Li Zhaonan Sun Fang Yuan Zhicheng Zhao Jiehong Zhang Baotong Zhang Hongyue Li Tong Liu Xiangchen Dai 《Journal of cellular and molecular medicine》2020,24(6):3438-3448
Indoleamine 2, 3-dioxygenase (IDO)-mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, ‘tryptophan depletion’ and ‘tryptophan metabolite accumulation’. The synergism between IDO+DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor-derived transplanted skin. This work demonstrates that the combination of IDO+DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs. 相似文献
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ChiWei Yeh WeiChieh Huang PangHung Hsu KunHai Yeh LiChin Wang Paul WeiChe Hsu HsiuChuan Lin YiNing Chen ShuChuan Chen ChenHsiang Yeang HsuehChi S Yen 《The EMBO journal》2021,40(7)
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or degrons, at their amino‐ or carboxyl‐termini are eliminated by the N‐ or C‐degron pathways, respectively. We aimed to elucidate the function of C‐degron pathways and to unveil how normal proteomes are exempt from C‐degron pathway‐mediated destruction. Our data reveal that C‐degron pathways remove mislocalized cellular proteins and cleavage products of deubiquitinating enzymes. Furthermore, the C‐degron and N‐degron pathways cooperate in protein removal. Proteome analysis revealed a shortfall in normal proteins targeted by C‐degron pathways, but not of defective proteins, suggesting proteolysis‐based immunity as a constraint for protein evolution/selection. Our work highlights the importance of protein termini for protein quality surveillance, and the relationship between the functional proteome and protein degradation pathways. 相似文献
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19.
Fang Yu Jiangbo Wei Xiaolong Cui Chunjie Yu Wei Ni Jrg Bungert Lizi Wu Chuan He Zhijian Qian 《Nucleic acids research》2021,49(10):5779
Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS. 相似文献
20.
Chen Jing-Jing Shen Jun-Xian Yu Zong-Hao Pan Chuan Han Fei Zhu Xiu-Ling Xu Hui Xu Rui-Ting Wei Tong-Yao Lu Ya-Ping 《Neurochemical research》2021,46(3):660-674
Neurochemical Research - Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint... 相似文献