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991.
p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate 总被引:6,自引:0,他引:6
Kunisaki R Ikawa S Maeda T Nakazaki Y Kurita R Harata M Shutoh Y Bai YS Soda Y Tanabe T Dohi T Kato R Ikawa Y Asano S Tani K 《The journal of gene medicine》2006,8(9):1121-1130
BACKGROUND: p51 (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti-cancer therapy. METHODS: In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti-oncogenesis in vitro and in vivo. RESULTS: Overexpression of p51A revealed an anti-proliferative effect in vitro in all the cancer cells examined in this study. The anchorage-dependent and -independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53-inducible genes, indicating that the mechanisms controlling p51- and p53-mediated tumor suppression differed. CONCLUSIONS: Our observations indicate that, although p51 exhibited reduced anti-oncogenetic effects compared with p53, it cooperatively enhanced the anti-tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy. 相似文献
992.
Rauma-Pinola T Pääkkö P Ilves M Serpi R Romppanen H Vuolteenaho O Ruskoaho H Hautala T 《The journal of gene medicine》2006,8(4):452-458
Arterial wall injury leads to inflammatory reaction and release of growth factors that may mediate intimal regrowth. It is hypothesized that the neointimal cells may originate from adventitial myofibroblasts, medial smooth muscle cells, or differentiated bone marrow derived cells. Adrenomedullin (AM), an auto/paracrine cardiovascular peptide that is secreted from fibroblasts, endothelial cells, and vascular smooth muscle cells, may have a regulatory role in the intimal regeneration. In order to investigate the role of AM in neointimal growth, stimulation of stem cell migration, and apoptosis, we overexpressed AM with recombinant adenovirus in a rat arterial injury model. The intimae were significantly thinner in the arteries treated with AM adenovirus compared to the control group. Intima/media ratios were 0.48 +/- 0.18 and 1.01 +/- 0.20 (P < 0.05) in the AM group and the control group, respectively. In addition, a significantly higher apoptotic index of neointimal cells was seen in the AM gene transfer group compared to the control (2.78 +/- 0.5 vs. 0.57 +/- 0.20, P < 0.01). The neointimal cells stained positive for alpha-smooth muscle actin and negative for desmin suggesting possible myofibroblast origin. Very few c-Kit+ or MDR1+ cells were detected 2 weeks after the injury. We conclude that AM overexpression inhibits neointimal growth. The inhibition is associated with enhanced apoptosis of the neointimal cells which may be of myofibroblast origin. 相似文献
993.
994.
Rodríguez-Hernández A Brea-Calvo G Fernández-Ayala DJ Cordero M Navas P Sánchez-Alcázar JA 《Apoptosis : an international journal on programmed cell death》2006,11(1):131-139
Chemotherapy-induced apoptosis by DNA-damaging drugs is thought to be generally dependent on the release of cytochrome c and the subsequent activation of caspase-9 and -3. However, the molecular mechanism of how damaged DNA triggers the apoptotic
process is not clear. To better understand the mechanisms underlying this process, we examined drug-induced apoptosis in cultured
H-460 cells. Using cell fractionation, western blotting, and immunofluorescence assays, we show that the activation of nuclear
caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis. Moreover,
we demonstrate that these events precede the release of cytochrome c and apoptotic inducing factor, and the activation of caspases 2, 8, 9 and 12. Together our results suggest that drugs acting
at the DNA level can initiate apoptosis via nuclear caspase activation.
An erratum to this article is available at . 相似文献
995.
996.
Pioglitazone, a synthetic ligand for PPARγ, induces apoptosis in RB-deficient human colorectal cancer cells 总被引:1,自引:0,他引:1
Lee CJ Han JS Seo CY Park TH Kwon HC Jeong JS Kim IH Yun J Bae YS Kwak JY Park JI 《Apoptosis : an international journal on programmed cell death》2006,11(3):401-411
No published data are available about the expression of peroxisome proliferator-activated receptor γ (PPARγ) and the role
of PPARγ in retinoblastoma protein (RB)-deficient human colorectal cancer (CRC) cells (SNU-C4 and SNU-C2A). Our aim was to
investigate whether PPARγ is expressed in SNU-C4 and SNU-C2A cells and to elucidate possible molecular mechanisms underlying
the effect of pioglitazone, a synthetic ligand for PPARγ, on cell growth in these cell lines. RT-PCR and Western blot analysis
showed that both human CRC cell lines expressed PPARγ mRNA and protein. Pioglitazone inhibited the cell growth of both cell
lines through G2/M phase block and apoptosis. In addition, pioglitazone caused a down-regulation of the X chromosome-linked
inhibitor of apoptosis (XIAP), Bcl-2, and cyclooxygenase-2 (COX-2) under conditions leading to PPARγ down-regulation. These
results suggest that pioglitazone may have therapeutic relevance or significance in the treatment of human CRC, and the down-regulation
of XIAP, Bcl-2, and COX-2 may contribute to pioglitazone-induced apoptosis in these and other RB-deficient cell lines and
tumors. 相似文献
997.
998.
999.
Cathepsin-regulated apoptosis 总被引:6,自引:0,他引:6
Chwieralski CE Welte T Bühling F 《Apoptosis : an international journal on programmed cell death》2006,11(2):143-149
Apoptosis can be mediated by different mechanisms. There is growing evidence that different proteolytic enzymes are involved
in the regulation of apoptosis. Cathepsins are proteases which, under physiologic conditions, are localized intralysosomally.
In response to certain signals they are released from the lysosomes into the cytoplasm where they trigger apoptotic cell death
via various pathways, including the activation of caspases or the release of proapoptotic factors from the mitochondria. Here,
we review different mechanisms that induce the release of lysosomal enzymes, and the functional relevance of defined cathepsins
in defined models of apoptosis. 相似文献
1000.
Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis 总被引:1,自引:1,他引:0