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排序方式: 共有493条查询结果,搜索用时 203 毫秒
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William Ka Kei Wu Joseph Jao Yiu Sung Ka Fai To Le Yu Hai Tao Li Zhi Jie Li Kin Man Chu Jun Yu Chi Hin Cho 《Journal of cellular physiology》2010,223(1):178-186
The human cathelicidin LL‐37, a pleiotropic host defense peptide, is down‐regulated in gastric adenocarcinomas. We therefore investigated whether this peptide suppresses gastric cancer growth. LL‐37 lowered gastric cancer cell proliferation and delayed G1‐S transition in vitro and inhibits the growth of gastric cancer xenograft in vivo. In this connection, LL‐37 increased the tumor‐suppressing bone morphogenetic protein (BMP) signaling, manifested as an increase in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of p21Waf1/Cip1. The anti‐mitogenic effect, Smad1/5 phosphorylation, and p21Waf1/Cip1 up‐regulation induced by LL‐37 were reversed by the knockdown of BMP receptor II. The activation of BMP signaling was paralleled by the inhibition of chymotrypsin‐like and caspase‐like activity of proteasome. In this regard, proteasome inhibitor MG‐132 mimicked the effect of LL‐37 by up‐regulating BMP4 expression and Smad1/5 phosphorylation. Further analysis of clinical samples revealed that LL‐37 and p21Waf1/Cip1 mRNA expressions were both down‐regulated in gastric cancer tissues and their expressions were positively correlated. Collectively, we describe for the first time that LL‐37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome‐dependent mechanism. This unique biological activity may open up novel therapeutic avenue for the treatment of gastric cancer. J. Cell. Physiol. 223: 178–186, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
54.
Kin Chung Leung Billy C.S. Leung Tony S.K. Mok George G. Chen 《Experimental cell research》2010,316(20):3468-3477
Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI. 相似文献
55.
DiDonato M Krishna SS Schwarzenbacher R McMullan D Jaroszewski L Miller MD Abdubek P Agarwalla S Ambing E Axelrod H Biorac T Chiu HJ Deacon AM Elsliger MA Feuerhelm J Godzik A Grittini C Grzechnik SK Hale J Hampton E Haugen J Hornsby M Klock HE Knuth MW Koesema E Kreusch A Kuhn P Lesley SA Moy K Nigoghossian E Okach L Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2006,63(1):256-260
56.
Han GW Sri Krishna S Schwarzenbacher R McMullan D Ginalski K Elsliger MA Brittain SM Abdubek P Agarwalla S Ambing E Astakhova T Axelrod H Canaves JM Chiu HJ DiDonato M Grzechnik SK Hale J Hampton E Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Kreusch A Kuhn P Miller MD Morse AT Moy K Nigoghossian E Oommachen S Ouyang J Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J Wang X West B White A Wolf G Xu Q Hodgson KO Wooley J Deacon AM Godzik A 《Proteins》2006,64(4):1083-1090
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Oishi Y Arakawa T Tanimura A Itakura M Takahashi M Tajima Y Mizoguchi I Takuma T 《Histochemistry and cell biology》2006,125(3):273-281
We evaluated the role of VAMP-2/synaptobrevin, VAMP-7/TI-VAMP, and VAMP-8/endobrevin in exocytic pathways of HSY cells, a
human parotid epithelial cell line, by coexpressing these VAMP proteins tagged with green fluorescent protein (GFP) and human
growth hormone (hGH) as a secretory cargo. Exocytosis of hGH was constitutive and the fluorescent signal of hGH–GFP was observed
in the Golgi area and small vesicles quickly moving throughout the cytoplasm. The cytoplasmic vesicles containing hGH overlapped
well with VAMP-7-GFP, but did so scarcely with VAMP-2-GFP or VAMP-8-GFP. However, when the vesicle transport from the trans-Golgi network to the plasma membrane was arrested by incubation at 20°C for 2 h and then released by warming up to 37°C;
VAMP-2-GFP and hGH were clearly colocalized together in small cytoplasmic vesicles. Neither VAMP-7-GFP nor hGH–GFP was colocalized
with LAMP-1, a marker for lysosomes and late endosomes. These results suggest that (1) VAMP-2 can be one of the v-SNAREs for
constitutive exocytosis; (2) VAMP-7 is involved in the constitutive exocytosis as a slow, minor v-SNARE, but not in the lysosomal
transport; and (3) VAMP-8 is unlikely to be a v-SNARE for constitutive exocytosis in HSY cells. 相似文献
59.
Analysis of the requirements for pilus biogenesis at the outer membrane usher and the function of the usher C-terminus 总被引:2,自引:0,他引:2
Uropathogenic strains of Escherichia coli assemble type 1 and P pili to colonize the bladder and kidney respectively. These pili are prototype structures assembled by the chaperone/usher secretion pathway. In this pathway, a periplasmic chaperone works together with an outer membrane (OM) usher to control the folding of pilus subunits, their assembly into a pilus fibre and secretion of the fibre to the cell surface. The usher serves as the assembly and secretion platform in the OM. The usher has distinct functional domains, with the N-terminus providing the initial targeting site for chaperone-subunit complexes and the C-terminus required for subsequent stages of pilus biogenesis. In this study, we investigated the molecular interactions occurring at the usher during pilus biogenesis and the function of the usher C-terminus. We provide genetic and biochemical evidence that the usher functions as a complex in the OM and that interaction of the pilus adhesin with the usher is critical to prime the usher for pilus biogenesis. Analysis of C-terminal truncation and substitution mutants of the P pilus usher PapC demonstrated that the C-terminus is required for proper binding of chaperone-subunit complexes to the usher and plays an important role in assembly of complete pili. 相似文献
60.
Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways 总被引:10,自引:0,他引:10
Sun HY Wang NP Halkos M Kerendi F Kin H Guyton RA Vinten-Johansen J Zhao ZQ 《Apoptosis : an international journal on programmed cell death》2006,11(9):1583-1593
A sequence of intermittent interruptions of oxygen supply (i.e., postconditioning, Postcon) at reoxygenation reduces oxidant-induced
cardiomyocyte loss. This study tested the hypothesis that prevention of cardiomyocyte apoptosis by Postcon is mediated by
mitogen-activated protein kinases pathways. Primary cultured neonatal rat cardiomyocytes were exposed to 3 h hypoxia followed
by 6 h of reoxygenation. Cardiomyocytes were postconditioned by three cycles each of 5 min reoxygenation and 5 min hypoxia
after prolonged hypoxia. Relative to hypoxia alone, reoxygenation stimulated expression of JNKs and p38 kinases, corresponding
to increased activity of JNKs (phospho-c-Jun) and p38 (phospho-ATF2). The level of TNFα in cell lysates, activity of cytosolic
caspases-8, -3, expression of Bax and the number of apoptotic cardiomyocytes were increased while expression of Bcl-2 was
decreased with reoxygenation. Consistent with an attenuation in generation of superoxide anions detected by lucigenin-enhanced
chemiluminescence at early period of reoxygenation, treatment of cardiomyocytes with Postcon further reduced expression and
activity of JNKs and p38 kinases, level of TNFα, the frequency of apoptotic cells and expression of Bax. However, the inhibitory
effects of Postcon on these changes were lost when its application was delayed by 5 min after the start of reoxygenation.
Addition of a JNK/p38 stimulator, anisomycin into cardiomyocytes at the beginning of reoxygenation eliminated protection by
Postcon. These data suggest that 1) hypoxia/reoxygenation elicits cardiomyocyte apoptosis in conjunction with expression and
activation of JNK and p38 kinases, release of TNFα, activation of caspases, and an increase in imbalance of pro-/anti-apoptotic
proteins; 2) Postcon attenuates cardiomyocyte apoptosis, potentially mediated by inhibiting JNKs/p-38 signaling pathways and
reducing TNFα release and caspase expression. 相似文献