全文获取类型
收费全文 | 793篇 |
免费 | 58篇 |
国内免费 | 70篇 |
出版年
2024年 | 2篇 |
2023年 | 18篇 |
2022年 | 30篇 |
2021年 | 51篇 |
2020年 | 23篇 |
2019年 | 37篇 |
2018年 | 33篇 |
2017年 | 28篇 |
2016年 | 44篇 |
2015年 | 48篇 |
2014年 | 66篇 |
2013年 | 62篇 |
2012年 | 84篇 |
2011年 | 67篇 |
2010年 | 45篇 |
2009年 | 35篇 |
2008年 | 37篇 |
2007年 | 35篇 |
2006年 | 24篇 |
2005年 | 34篇 |
2004年 | 17篇 |
2003年 | 19篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 1篇 |
1991年 | 7篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有921条查询结果,搜索用时 31 毫秒
41.
Jinling Wang Xiaohui Peng Daowei Yang Mengyu Guo Xiao Xu Fengyue Yin Yu Wang Jiaqing Huang Linghui Zhan Zhongquan Qi 《Journal of cellular and molecular medicine》2022,26(2):563
Aresenic trioxide (ATO) is proven to be active against leukaemia cells by inducing apoptosis and differentiation. Even though ATO could effectively induce remissions of leukaemia cells, the drug resistance was observed occasionally. To further dissect the mechanism of ATO resistance, we selected the ATO‐resistant SH‐SY5Y cells and found that Bcl‐2 controlled the sensitivity of ATO in SH‐SY5Y cells. We report that necroptosis, autophagy, NF‐ƘB and MAPK signalling pathway are not involved in ATO‐induced apoptosis. Moreover, the ATO‐resistant cells showed distinct mitochondrial morphology compared with that of ATO‐sensitive cells. Intriguingly, nude mice‐bearing ATO‐sensitive cells derived xenograft tumours are more sensitive to ATO treatment compared with that of ATO‐resistant cells. These data demonstrate that cancer cells can acquire the ATO‐resistance ability by increasing the Bcl‐2 expression. 相似文献
42.
43.
X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway 总被引:34,自引:0,他引:34
Diao J Khine AA Sarangi F Hsu E Iorio C Tibbles LA Woodgett JR Penninger J Richardson CD 《The Journal of biological chemistry》2001,276(11):8328-8340
The X protein from a chronic strain of hepatitis B virus (HBx) was determined to inhibit Fas-mediated apoptosis and promote cell survival. Fas-mediated apoptosis is the major cause of hepatocyte damage during liver disease. Experiments demonstrated that cell death caused by anti-Fas antibodies was blocked by the expression of HBx in human primary hepatocytes and mouse embryo fibroblasts. This effect was also observed in mouse erythroleukemia cells that lacked p53, indicating that protection against Fas-mediated apoptosis was independent of p53. Components of the signal transduction pathways involved in this protection were studied. The SAPK/JNK pathway has previously been suggested to be a survival pathway for some cells undergoing Fas-mediated apoptosis, and kinase assays showed that SAPK activity was highly up-regulated in cells expressing the HBx protein. Normal mouse fibroblasts expressing HBx were protected from death, whereas identical fibroblasts lacking the SEK1 component from the SAPK pathway succumbed to Fas-mediated apoptosis, whether HBx was present or not. Assays showed that caspase 3 and 8 activities and the release of cytochrome c from mitochondria were inhibited, in the presence of HBx, following stimulation with anti-Fas antibodies. Coprecipitation and confocal immunofluorescence microscopy experiments demonstrated that HBx localizes with a cytoplasmic complex containing MEKK1, SEK1, SAPK, and 14-3-3 proteins. Finally, mutational analysis of HBx demonstrated that a potential binding region for 14-3-3 proteins was essential for induction of SAPK/JNK activity and protection from Fas-mediated apoptosis. 相似文献
44.
45.
Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study 总被引:1,自引:0,他引:1
46.
47.
Wang R Zhang L Bolstad J Diao N Brown C Ruest L Welch W Williams AJ Chen SR 《The Journal of biological chemistry》2003,278(51):51557-51565
Despite the pivotal role of ryanodine in ryanodine receptor (RyR) research, the molecular basis of ryanodine-RyR interaction remains largely undefined. We investigated the role of the proposed transmembrane helix TM10 in ryanodine interaction and channel function. Each amino acid residue within the TM10 sequence, 4844IIFDITFFFFVIVILLAIIQGLII4867, of the mouse RyR2 was mutated to either alanine or glycine. Mutants were expressed in human embryonic kidney 293 cells, and their properties were assessed. Mutations D4847A, F4850A, F4851A, L4858A, L4859A, and I4866A severely curtailed the release of intracellular Ca2+ in human embryonic kidney 293 cells in response to extracellular caffeine and diminished [3H]ryanodine binding to cell lysates. Mutations F4846A, T4849A, I4855A, V4856A, and Q4863A eliminated or markedly reduced [3H]ryanodine binding, but cells expressing these mutants responded to extracellular caffeine by releasing stored Ca2+. Interestingly these two groups of mutants, each with similar properties, are largely located on opposite sides of the predicted TM10 helix. Single channel analyses revealed that mutation Q4863A dramatically altered the kinetics and apparent affinity of ryanodine interaction with single RyR2 channels and abolished the effect of ryanodol, an analogue of ryanodine, whereas the single channel conductance of the Q4863A mutant and its responses to caffeine, ATP, and Mg2+ were comparable to those of the wild type channels. Furthermore the effect of ryanodine on single Q4863A mutant channels was influenced by the transmembrane holding potential. Together these results suggest that the TM10 sequence and in particular the Q4863 residue constitute an important determinant of ryanodine interaction. 相似文献
48.
Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate) 总被引:5,自引:0,他引:5
Zaneveld LJ Waller DP Anderson RA Chany C Rencher WF Feathergill K Diao XH Doncel GF Herold B Cooper M 《Biology of reproduction》2002,66(4):886-894
Host cell infection by sexually transmitted disease (STD)-causing microbes and fertilization by spermatozoa may have some mechanisms in common. If so, certain noncytotoxic agents could inhibit the functional activity of both organisms. High molecular mass poly(sodium 4-styrenesulfonate) (T-PSS) may be one of these compounds. T-PSS alone (1 mg/ml) or in a gel (2% or 5% T-PSS) completely prevented conception in the rabbit. Contraception was not due to sperm cytotoxicity or to an effect on sperm migration. However, T-PSS inhibited sperm hyaluronidase (IC(50) = 5.3 microg/ml) and acrosin (IC(50) = 0.3 microg/ml) and caused the loss of acrosomes from spermatozoa (85% maximal loss by 0.5 microg/ml). T-PSS (5% in gel) also reduced sperm penetration into bovine cervical mucus (73% inhibition by 1 mg gel/ml). T-PSS (5% in gel) inhibited human immunodeficiency virus (HIV; IC(50)= 16 microg gel/ml) and herpes simplex viruses (HSV-1 and HSV-2; IC(50) = 1.3 and 1.0 microg gel/ml, respectively). The drug showed high efficacy against a number of clinical isolates and laboratory strains. T-PSS (5% in gel) also inhibited Neisseria gonorrhea (IC(50) < 1.0 gel/ml) and Chlamydia trachomatis (IC(50) = 1.2 microg gel/ml) but had no effect on lactobacilli. These results imply that T-PSS is an effective functional inhibitor of both spermatozoa and certain STD-causing microbes. The noncytotoxic nature should make T-PSS safe for vaginal use. T-PSS was nonmutagenic in vitro and possessed an acute oral toxicity of >5 g/kg (rat). Gel with 10% T-PSS did not irritate the skin or penile mucosa (rabbit) and caused no dermal sensitization (guinea pig). Vaginal administration of the 5% T-PSS gel to the rabbit for 14 consecutive days caused no systemic toxicity and only mild (acceptable) vaginal irritation. T-PSS in gel form is worthy of clinical evaluation as a vaginal contraceptive HIV/STD preventative. 相似文献
49.
50.
The distinctive gymnosperm genus Ephedra is sometimes considered to have originated over 200 million years (Myr) ago on the basis of "ephedroid" fossil pollen. In this article we estimate the age of extant Ephedra using chloroplast rbcL gene sequences. Relative rate tests fail to reject the null hypothesis of equal rates of nucleotide substitution of the rbcL sequences among three landmark lineages (Gnetales, Pinaceae, and Ginkgo). The most divergent sequences we have found in Ephedra differ by only 7 bp for an 1,110 bp region of rbcL sequence, whereas the differences among genera range from 92 to 107 bp in Gnetales and from 35 to 92 bp in Pinaceae. Using three landmark events, the age of extant Ephedra is estimated to be approximately 8-32 Myr. Our result is consistent with the current distribution of many Ephedra species in geologically recent habitats and points out difficulties in the identification of older ephedroid pollen fossils with the modern genus Ephedra. 相似文献