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《Molecular & cellular proteomics : MCP》2019,18(1):151-161
Highlights
- •New MALDI MS imaging sample preparation workflow reveals tissue protease activity.
- •Differential time- and inhibitor concentration-dependence confirm active proteases.
- •Mouse gastric tumor displays high protease activity compared to surrounding tissue.
- •Proteomic data and biochemical protease activity assay support MALDI MSI results.
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Jin CH Krishnaiah M Sreenu D Subrahmanyam VB Rao KS Mohan AV Park CY Son JY Sheen YY Kim DK 《Bioorganic & medicinal chemistry letters》2011,21(20):6049-6053
A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. 相似文献
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The majority of prostate cancer-related deaths are associated with advanced and metastatic malignancies. Although anoikis resistance has been recognized as one of the hallmarks of metastatic prostate malignancies, the molecular events that cause anoikis resistance are poorly understood. In this study, we found that the detachment of PC-3 prostate cancer cells caused a time-dependent increase in the expression level of the leukotriene B4 receptor-2 (BLT2) and that BLT2 played a critical role in establishing anoikis resistance in these cells. Blocking BLT2 with the pharmacological inhibitor or with RNAi knockdown clearly abolished anoikis resistance and resulted in severe apoptotic death. Additionally, we demonstrated that the activation of NADPH oxidase (NOX) and subsequent generation of reactive oxygen species (ROS) were downstream of BLT2 signaling and led to the activation of NF-κB, thus establishing anoikis resistance during cell detachment. Furthermore, we observed that the ectopic expression of BLT2 in normal prostate PWR-1E cells rendered the cells resistant to anoikis and apparently diminished apoptotic cell death following detachment. Taken together, our results suggest that BLT2-NOX-ROS-NF-κB cascade induction during detachment confers a novel mechanism of anoikis resistance in prostate cancer cells and potentially contributes to prostate cancer progression. LY255283相似文献
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Raghunath Chatterjee Charles Vinson 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2012,1819(7):763-770
CG methylation is an epigenetically inherited chemical modification of DNA found in plants and animals. In mammals it is essential for accurate regulation of gene expression and normal development. Mammalian genomes are depleted for the CG dinucleotide, a result of the chemical deamination of methyl-cytosine in CG resulting in TpG. Most CG dinucleotides are methylated, but ~ 15% are unmethylated. Five percent of CGs cluster into ~ 20,000 regions termed CG islands (CGI) which are generally unmethylated. About half of CGIs are associated with housekeeping genes. In contrast, the gene body, repeats and transposable elements in which CGs are generally methylated. Unraveling the epigenetic machinery operating in normal cells is important for understanding the epigenetic aberrations that are involved in human diseases including cancer. With the advent of high-throughput sequencing technologies, it is possible to identify the CG methylation status of all 30 million unique CGs in the human genome, and monitor differences in distinct cell types during differentiation and development. Here we summarize the present understanding of DNA methylation in normal cells and discuss recent observations that CG methylation can have an effect on tissue specific gene expression. We also discuss how aberrant CG methylation can lead to cancer. This article is part of a Special Issue entitled: Chromatin in time and space. 相似文献
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In the present study, the whole-cell patch-clamp technique was applied to follow the inhibitory effect of genistein — a tyrosine
kinase inhibitor and a natural anticancer agent—on the activity of voltage-gated potassium channels Kv1.3 expressed in human
T lymphocytes (TL). Obtained data provide evidence that genistein application in the concentration range of 1–80 μM reversibly decreased the whole-cell potassium currents in TL in a concentration-dependent manner to about 0.23 of the control
value. The half-blocking concentration range of genistein was from 10 to 40 μM. The current inhibition was correlated in time with a significant decrease of the current activation rate. The steady-state
activation of the currents was unchanged upon application of genistein, as was the inactivation rate. The inhibitory effect
of genistein on the current amplitude and activation kinetics was voltage-independent. The current inhibition was not changed
significantly in the presence of 1 mM of sodium orthovanadate, a tyrosine phosphatase inhibitor. Application of daidzein, an inactive genistein analogue, did not
affect significantly either the current amplitudes or the activation kinetics. Possible mechanisms of the observed phenomena
and their significance for genistein-induced inhibition of cancer cell proliferation are discussed. 相似文献
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Karl Deacon David Onion Rajendra Kumari Susan A. Watson Alan J. Knox 《The Journal of biological chemistry》2012,287(47):39967-39981