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Tau is a microtubule-associated protein implicated in neurodegenerative tauopathies. Six tau isoforms are generated from a single gene through alternative splicing of exons 2, 3 and 10 in human brain. Differential expression of tau isoforms has been detected in different brain areas, during neurodevelopment and in neurodegenerative disorders. However, the biological significance of different tau isoforms is not clear. Here, we investigated the individual effect of six different isoforms of tau on cell proliferation and the possible mechanisms by transient expression of eGFP-labeled tau isoform plasmid in N2a cells. Our study showed the transfection efficiency was comparable between different isoforms of tau by examining GFP expression. Compared with other isoforms, we found expression of 1N3R-tau significantly inhibited cell proliferation by Cell Counting Kit-8 assay and BrdU incorporation. Flow cytometry analysis further showed expression of 1N3R-tau induced S phase arrest. Compared with the longest isoform of tau, expression of 1N3R-tau induced cyclin E translocation from the nuclei to cytoplasm, while it did not change the level of cell cycle checkpoint proteins. These data indicate that 1N3R-tau inhibits cell proliferation through inducing S phase arrest.  相似文献   
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Accurate estimation of forest biomass C stock is essential to understand carbon cycles. However, current estimates of Chinese forest biomass are mostly based on inventory-based timber volumes and empirical conversion factors at the provincial scale, which could introduce large uncertainties in forest biomass estimation. Here we provide a data-driven estimate of Chinese forest aboveground biomass from 2001 to 2013 at a spatial resolution of 1 km by integrating a recently reviewed plot-level ground-measured forest aboveground biomass database with geospatial information from 1-km Moderate-Resolution Imaging Spectroradiometer (MODIS) dataset in a machine learning algorithm (the model tree ensemble, MTE). We show that Chinese forest aboveground biomass is 8.56 Pg C, which is mainly contributed by evergreen needle-leaf forests and deciduous broadleaf forests. The mean forest aboveground biomass density is 56.1 Mg C ha−1, with high values observed in temperate humid regions. The responses of forest aboveground biomass density to mean annual temperature are closely tied to water conditions; that is, negative responses dominate regions with mean annual precipitation less than 1300 mm y−1 and positive responses prevail in regions with mean annual precipitation higher than 2800 mm y−1. During the 2000s, the forests in China sequestered C by 61.9 Tg C y−1, and this C sink is mainly distributed in north China and may be attributed to warming climate, rising CO2 concentration, N deposition, and growth of young forests.  相似文献   
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In biomedical or public health research, it is common for both survival time and longitudinal categorical outcomes to be collected for a subject, along with the subject’s characteristics or risk factors. Investigators are often interested in finding important variables for predicting both survival time and longitudinal outcomes which could be correlated within the same subject. Existing approaches for such joint analyses deal with continuous longitudinal outcomes. New statistical methods need to be developed for categorical longitudinal outcomes. We propose to simultaneously model the survival time with a stratified Cox proportional hazards model and the longitudinal categorical outcomes with a generalized linear mixed model. Random effects are introduced to account for the dependence between survival time and longitudinal outcomes due to unobserved factors. The Expectation–Maximization (EM) algorithm is used to derive the point estimates for the model parameters, and the observed information matrix is adopted to estimate their asymptotic variances. Asymptotic properties for our proposed maximum likelihood estimators are established using the theory of empirical processes. The method is demonstrated to perform well in finite samples via simulation studies. We illustrate our approach with data from the Carolina Head and Neck Cancer Study (CHANCE) and compare the results based on our simultaneous analysis and the separately conducted analyses using the generalized linear mixed model and the Cox proportional hazards model. Our proposed method identifies more predictors than by separate analyses.  相似文献   
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Multiple studies have confirmed the pro‐oncogenic effects of PAX3 in an array of cancers, but its role in prostate cancer (PCa) remains largely undefined. The aim of this study is to investigate the role of PAX3 in PCa. PAX3 expression was compared between PCa tumor tissue and nontumor tissues and PCa cell lines and normal prostate epithelial cells (PNT2) by western blot analysis and immunohistochemistry staining. MTT and immunofluorescence assays were used to detect PCa cell proliferation. Flow cytometry was used to evaluate cell apoptosis in PCa. Transwell assays were used for the determination of cell migration and PCa cell invasion. PAX3 expression was higher in PCa tissues and human PCa cell lines. Moreover, PAX3 silencing inhibited the proliferation, metastasis, and epithelial–mesenchymal transition (EMT) of PCa cells, and increased the rates of apoptosis. PAX3 silencing inhibited transforming growth factor‐β (TGF‐β)/Smad signaling in PCa cells. The effects of si‐PAX3 on the proliferation, apoptosis, metastasis, and EMT of PCa cells were alleviated by TGF‐β1 treatment. PAX3 silencing inhibits PCa progression through the inhibition of TGF‐β/Smad signaling. This reveals PAX3 as a novel biomarker and therapeutic target for future PCa treatments.  相似文献   
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Many double-stranded RNA (dsRNA) viruses are capable of transcribing and capping RNA within a stable icosahedral viral capsid. The turret of turreted dsRNA viruses belonging to the family Reoviridae is formed by five copies of the turret protein, which contains domains with both 7-N-methyltransferase and 2′-O-methyltransferase activities, and serves to catalyze the methylation reactions during RNA capping. Cypovirus of the family Reoviridae provides a good model system for studying the methylation reactions in dsRNA viruses. Here, we present the structure of a transcribing cypovirus to a resolution of ~ 3.8 Å by cryo-electron microscopy. The binding sites for both S-adenosyl-l-methionine and RNA in the two methyltransferases of the turret were identified. Structural analysis of the turret in complex with RNA revealed a pathway through which the RNA molecule reaches the active sites of the two methyltransferases before it is released into the cytoplasm. The pathway shows that RNA capping reactions occur in the active sites of different turret protein monomers, suggesting that RNA capping requires concerted efforts by at least three turret protein monomers. Thus, the turret structure provides novel insights into the precise mechanisms of RNA methylation.  相似文献   
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