全文获取类型
收费全文 | 1188篇 |
免费 | 2篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 8篇 |
丛书文集 | 36篇 |
教育与普及 | 21篇 |
理论与方法论 | 4篇 |
现状及发展 | 75篇 |
研究方法 | 186篇 |
综合类 | 869篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 3篇 |
2020年 | 2篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 74篇 |
2011年 | 112篇 |
2010年 | 30篇 |
2009年 | 7篇 |
2008年 | 106篇 |
2007年 | 102篇 |
2006年 | 94篇 |
2005年 | 84篇 |
2004年 | 80篇 |
2003年 | 77篇 |
2002年 | 62篇 |
2001年 | 41篇 |
2000年 | 85篇 |
1999年 | 26篇 |
1998年 | 4篇 |
1997年 | 11篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
1971年 | 4篇 |
1970年 | 13篇 |
1966年 | 2篇 |
1964年 | 1篇 |
1960年 | 1篇 |
1959年 | 13篇 |
1958年 | 22篇 |
1957年 | 16篇 |
1956年 | 6篇 |
1955年 | 8篇 |
1954年 | 9篇 |
1948年 | 11篇 |
1947年 | 1篇 |
排序方式: 共有1199条查询结果,搜索用时 31 毫秒
261.
262.
263.
RGD peptides induce apoptosis by direct caspase-3 activation 总被引:36,自引:0,他引:36
Buckley CD Pilling D Henriquez NV Parsonage G Threlfall K Scheel-Toellner D Simmons DL Akbar AN Lord JM Salmon M 《Nature》1999,397(6719):534-539
Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis. 相似文献
264.
265.
Liu G Parant JM Lang G Chau P Chavez-Reyes A El-Naggar AK Multani A Chang S Lozano G 《Nature genetics》2004,36(1):63-68
The p53 protein integrates multiple upstream signals and functions as a tumor suppressor by activating distinct downstream genes. At the cellular level, p53 induces apoptosis, cell cycle arrest and senescence. A rare mutant form of p53 with the amino acid substitution R175P, found in human tumors, is completely defective in initiating apoptosis but still induces cell cycle arrest. To decipher the functional importance of these pathways in spontaneous tumorigenesis, we used homologous recombination to generate mice with mutant p53-R172P (the mouse equivalent of R175P in humans). Mice inheriting two copies of this mutation (Trp53(515C/515C)) escape the early onset of thymic lymphomas that characterize Trp53-null mice. At 7 months of age, 90% of Trp53-null mice had died, but 85% of Trp53(515C/515C) mice were alive and tumor-free, indicating that p53-dependent apoptosis was not required for suppression of early onset of spontaneous tumors. The lymphomas and sarcomas that eventually developed in Trp53(515C/515C) mice retained a diploid chromosome number, in sharp contrast to aneuploidy observed in tumors and cells from Trp53-null mice. The ability of mutant p53-R172P to induce a partial cell cycle arrest and retain chromosome stability are crucial for suppression of early onset tumorigenesis. 相似文献
266.
Gissen P Johnson CA Morgan NV Stapelbroek JM Forshew T Cooper WN McKiernan PJ Klomp LW Morris AA Wraith JE McClean P Lynch SA Thompson RJ Lo B Quarrell OW Di Rocco M Trembath RC Mandel H Wali S Karet FE Knisely AS Houwen RH Kelly DA Maher ER 《Nature genetics》2004,36(4):400-404
ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion. 相似文献
267.
Eight glacial cycles from an Antarctic ice core 总被引:9,自引:0,他引:9
Augustin L Barbante C Barnes PR Barnola JM Bigler M Castellano E Cattani O Chappellaz J Dahl-Jensen D Delmonte B Dreyfus G Durand G Falourd S Fischer H Flückiger J Hansson ME Huybrechts P Jugie G Johnsen SJ Jouzel J Kaufmann P Kipfstuhl J Lambert F Lipenkov VY Littot GC Longinelli A Lorrain R Maggi V Masson-Delmotte V Miller H Mulvaney R Oerlemans J Oerter H Orombelli G Parrenin F Peel DA Petit JR Raynaud D Ritz C Ruth U Schwander J Siegenthaler U Souchez R Stauffer B Steffensen JP Stenni B 《Nature》2004,429(6992):623-628
The Antarctic Vostok ice core provided compelling evidence of the nature of climate, and of climate feedbacks, over the past 420,000 years. Marine records suggest that the amplitude of climate variability was smaller before that time, but such records are often poorly resolved. Moreover, it is not possible to infer the abundance of greenhouse gases in the atmosphere from marine records. Here we report the recovery of a deep ice core from Dome C, Antarctica, that provides a climate record for the past 740,000 years. For the four most recent glacial cycles, the data agree well with the record from Vostok. The earlier period, between 740,000 and 430,000 years ago, was characterized by less pronounced warmth in interglacial periods in Antarctica, but a higher proportion of each cycle was spent in the warm mode. The transition from glacial to interglacial conditions about 430,000 years ago (Termination V) resembles the transition into the present interglacial period in terms of the magnitude of change in temperatures and greenhouse gases, but there are significant differences in the patterns of change. The interglacial stage following Termination V was exceptionally long--28,000 years compared to, for example, the 12,000 years recorded so far in the present interglacial period. Given the similarities between this earlier warm period and today, our results may imply that without human intervention, a climate similar to the present one would extend well into the future. 相似文献
268.
Several lines of evidence have recently reinforced the hypothesis that an ocean existed on early Mars. Carbonates are accordingly expected to have formed from oceanic sedimentation of carbon dioxide from the ancient martian atmosphere. But spectral imaging of the martian surface has revealed the presence of only a small amount of carbonate, widely distributed in the martian dust. Here we examine the feasibility of carbonate synthesis in ancient martian oceans using aqueous equilibrium calculations. We show that partial pressures of atmospheric carbon dioxide in the range 0.8-4 bar, in the presence of up to 13.5 mM sulphate and 0.8 mM iron in sea water, result in an acidic oceanic environment with a pH of less than 6.2. This precludes the formation of siderite, usually expected to be the first major carbonate mineral to precipitate. We conclude that extensive interaction between an atmosphere dominated by carbon dioxide and a lasting sulphate- and iron-enriched acidic ocean on early Mars is a plausible explanation for the observed absence of carbonates. 相似文献
269.
Preparation of poly (methyl methacrylate)/nanometer calcium carbonate composite by in-situ emulsion polymerization 总被引:1,自引:0,他引:1
Methyl methacrylate (MMA) emulsion polymerization in the presence of nanometer calcium carbonate(nano-CaCO3) surface modified with γ-methacryloxypropyltrimethoxysilane (MPTMS) was carried out to prepare poly (methyl methacrylate) (PMMA)/nano-CaCO3 composite. The reaction between nano-CaCO3 and MPTMS, and the grafting of PMMA onto nano-CaCO3 were confirmed by infrared spectrum. The grafting ratio and grafting efficiency of PMMA on nano-CaCO3 modified with MPTMS were much higher than that on nano-CaCO3 modified with stearic acid. The grafting ratio of PMMA increased as the weight ratio between MMA and nano-CaCO3 increased, while the grafting efficiency of PMMA decreased. Transmission electron micrograph showed that nano-CaCO3 covered with PMMA was formed by in-situ emulsion polymerization. 相似文献
270.
Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity 总被引:5,自引:0,他引:5
To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37, human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418. The biological expression of rhIL-18 was tested by RT-PCR and ELISA method; nude mice were injected with Bcap37 cell with or without the hIL-18 gene. The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3+/-4.5 pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth. These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine; the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity. The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine. 相似文献