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91.
Jennifer L. Jacobi Bo Yang Xu Li Anna K. Menze Sara M. Laurentz Elsa M. Janle Mario G. Ferruzzi George P. McCabe Clint Chapple Ann L. Kirchmaier 《PloS one》2016,11(2)
The plant secondary metabolite and common food additive dihydrocoumarin (DHC) is an inhibitor of the Sirtuin family of NAD+-dependent deacetylases. Sirtuins are key regulators of epigenetic processes that maintain silent chromatin in yeast and have been linked to gene expression, metabolism, apoptosis, tumorogenesis and age-related processes in multiple organisms, including humans. Here we report that exposure to the polyphenol DHC led to defects in several Sirtuin-regulated processes in budding yeast including the establishment and maintenance of Sir2p-dependent silencing by causing disassembly of silent chromatin, Hst1p-dependent repression of meiotic-specific genes during the mitotic cell cycle. As both transient and prolonged exposure to environmental and dietary factors have the potential to lead to heritable alterations in epigenetic states and to modulate additional Sirtuin-dependent phenotypes, we examined the bioavailability and digestive stability of DHC using an in vivo rat model and in vitro digestive simulator. Our analyses revealed that DHC was unstable during digestion and could be converted to melilotic acid (MA), which also caused epigenetic defects, albeit less efficiently. Upon ingestion, DHC was observed primarily in intestinal tissues, but did not accumulate over time and was readily cleared from the animals. MA displayed a wider tissue distribution and, in contrast to DHC, was also detected in the blood plasma, interstitial fluid, and urine, implying that the conversion of DHC to the less bioactive compound, MA, occurred efficiently in vivo. 相似文献
92.
Dongshi Wan Ailan Wang Xu Zhang Zhaofeng Wang Zhonghu Li 《Biochemical Systematics and Ecology》2011,39(4-6):651-659
It is suggested that gene duplication plays an important role in adaptation and evolution of plants. In this study, we examined whether the genus Rheum, with extensive diversification in the Qinghai-Tibeten Plateau (QTP) and adjacent regions, possessed the duplication of the chalcone synthase (CHS) genes and whether it underwent positive evolution. Here we cloned CHS-like genes from 16 Rheum species. Phylogenetic analyses suggested that CHS-like genes from Rheum comprised two monophyletic lineages (subfamilies), both of which were sisters to another related genus. The results showed that a genus-specific duplication occurred after this genus originated. The comparison of non-synonymous/synonymous substitution ratios between the two lineages in Rheum further indicated that a few sites along the duplicate branch underwent positive selection. The findings indicate that the duplication of Rheum species could contribute to their adaptive ability to rapidly changing environments which was resulted from the large-scale uplifts stages of QTP. 相似文献
93.
Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress 总被引:3,自引:0,他引:3
94.
Wandong Zhang Katerina V. Savelieva David T. Tran Vladimir M. Pogorelov Emily B. Cullinan Kevin B. Baker Kenneth A. Platt Sean Hu Indrani Rajan Nianhua Xu Thomas H. Lanthorn 《PloS one》2012,7(9)
Receptor tyrosine phosphatase gamma (PTPRG, or RPTPγ) is a mammalian receptor-like tyrosine phosphatase which is highly expressed in the nervous system as well as other tissues. Its function and biochemical characteristics remain largely unknown. We created a knockdown (KD) line of this gene in mouse by retroviral insertion that led to 98–99% reduction of RPTPγ gene expression. The knockdown mice displayed antidepressive-like behaviors in the tail-suspension test, confirming observations by Lamprianou et al. 2006. We investigated this phenotype in detail using multiple behavioral assays. To see if the antidepressive-like phenotype was due to the loss of phosphatase activity, we made a knock-in (KI) mouse in which a mutant, RPTPγ C1060S, replaced the wild type. We showed that human wild type RPTPγ protein, expressed and purified, demonstrated tyrosine phosphatase activity, and that the RPTPγ C1060S mutant was completely inactive. Phenotypic analysis showed that the KI mice also displayed some antidepressive-like phenotype. These results lead to a hypothesis that an RPTPγ inhibitor could be a potential treatment for human depressive disorders. In an effort to identify a natural substrate of RPTPγ for use in an assay for identifying inhibitors, “substrate trapping” mutants (C1060S, or D1028A) were studied in binding assays. Expressed in HEK293 cells, these mutant RPTPγs retained a phosphorylated tyrosine residue, whereas similarly expressed wild type RPTPγ did not. This suggested that wild type RPTPγ might auto-dephosphorylate which was confirmed by an in vitro dephosphorylation experiment. Using truncation and mutagenesis studies, we mapped the auto-dephosphorylation to the Y1307 residue in the D2 domain. This novel discovery provides a potential natural substrate peptide for drug screening assays, and also reveals a potential functional regulatory site for RPTPγ. Additional investigation of RPTPγ activity and regulation may lead to a better understanding of the biochemical underpinnings of human depression. 相似文献
95.
Baohua Cheng Xinxin Yang Chengchun Chen Danfu Cheng Xudong Xu Xuewen Zhang 《Neurochemical research》2010,35(3):444-451
Numerous studies show that D-β-Hydroxybutyrate (DβHB) is neuroprotective. The present study was to explore the neuroprotective
effects of DβHB against the cell death and apoptosis induced by 1-methyl-4-phenylpyridinium ion (MPP+) in PC12 cells. PC12
cells were pretreated with DβHB and followed by MPP+ exposure. The cell viability was determined by MTT assay. The morphological
characteristics of apoptosis was observed by Acridine Orange (AO) staining and apoptotic rates were measured by flow cytometer.
The product of lipid peroxidation, malondialdehyde (MDA), was measured using thiobarbituric acid method. The mitochondrial
membrane potential (MMP), intracellular ROS and total glutathione were detected by microplate reader. In PC12 cells, pretreatment
with DβHB significantly reduced MPP+-induced the decrease of cell viability. AO staining and flow cytometric analysis found
DβHB inhibited MPP+-induced apoptosis. The measurement of MDA formation showed that DβHB alleviated lipid peroxidation induced
by MPP+. The loss of MMP induced by MPP+ was preventive by DβHB. The changes of intracellular ROS and total glutathione induced
by MPP+ were reversed by DβHB. DβHB protected PC12 cells against MPP+-induced death and apoptosis. 相似文献
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100.
Arsenite efflux is not enhanced in the arsenate-tolerant phenotype of Holcus lanatus 总被引:1,自引:0,他引:1
B. Logoteta X. Y. Xu M. R. Macnair S. P. McGrath F. J. Zhao 《The New phytologist》2009,183(2):340-348