全文获取类型
收费全文 | 746篇 |
免费 | 77篇 |
出版年
2022年 | 5篇 |
2021年 | 7篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 15篇 |
2014年 | 25篇 |
2013年 | 55篇 |
2012年 | 29篇 |
2011年 | 36篇 |
2010年 | 19篇 |
2009年 | 16篇 |
2008年 | 32篇 |
2007年 | 37篇 |
2006年 | 28篇 |
2005年 | 36篇 |
2004年 | 36篇 |
2003年 | 40篇 |
2002年 | 50篇 |
2001年 | 40篇 |
2000年 | 22篇 |
1999年 | 22篇 |
1998年 | 15篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 22篇 |
1991年 | 22篇 |
1990年 | 14篇 |
1989年 | 13篇 |
1988年 | 12篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 10篇 |
1979年 | 4篇 |
1978年 | 9篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 2篇 |
排序方式: 共有823条查询结果,搜索用时 421 毫秒
41.
The effects of inhibition of protein synthesis on the cell size distributions of rel+ and relA- derivatives of Escherichia coli K-12 were determined. Amino acid deprivation resulted in a reduction in the cell sizes of rel+ strains but not of relA- strains. Treatment with chloramphenicol (CAM) did not alter the size distributions of either rel+ or relA- strains except when they were rel+ dap-. CAM treatment of rel+ dap- strains resulted in an increase in cell size. It is proposed that these results reflect differences in the structures of the cell envelopes of rel+ and relA- bacteria. 相似文献
42.
43.
Poly-β-1-naphthylmethyl-L -aspartate and copolymers of β-1-naphthylmethyl-L -aspartate and γ-benzyl-L -glutamate were prepared. From the results obtained by a study of infrared and circular dichroism spectra, poly-β-1-naphthylmethyl-L -aspartate was found to be a left-handed α-helix both in the solid state and in solution. The fluorescence spectra of these polymers showed excimer emission of the naphthyl chromophores and gave some information about the arrangement of the side-chain chromophores. By optical titration experiments, it was found that an increasing amount of β-1-naphthylmethyl-L -aspartate residues in the copolymers induces a progressive instability of the helical structure. 相似文献
44.
Y. Ohta R. Shinohara I. Ishiguro 《Redox report : communications in free radical research》2013,18(5):339-344
SummaryThe role of the prosthetic groups (FAD and FMN) of NADPH-cytochrome P450 reductase (P450 reductase)in 3-hydroxyanthranilamide (3-OH An.Amide)-catalyzed, NADPH-dependent superoxide anion (O2-) production via the reductase was examined using the native and FMN-depleted preparations of P450 reductase which was partially purified from rat liver microsomes. NADPH-dependent O2-production by the FMN-depleted preparation was about 10% of that by the native preparation. 3-OH An. Amide-catalyzed, NADPH-dependent O2-production by the FMN-depleted preparation was less than 10% of that by the native preparation. FMN supplementation returned O2-production to near normal. We observed the same results for NADPH oxidation and hydrogen peroxide formation. O2-production, NADPH oxidation, and hydrogen peroxide formation were inhibited by native superoxide dismutase (SOD), but not by boiled, denatured SOD. These results indicate that the prosthetic groups, especially FMN, of P450 reductase play a critical role in 3-OH An.Amide-catalyzed, NADPH-dependent O2-production via the reductase. 相似文献
45.
Junpei Ishiguro Kenta Shibahara Yumi Ueda Kei Nakamura 《Molecular genetics and genomics : MGG》2013,288(1-2):63-75
TOR (target of rapamycin) signaling regulates cell growth and division in response to environmental stimuli such as the availability of nutrients and various forms of stress. The vegetative growth of fission yeast cells, unlike other eukaryotic cells, is not inhibited by treatment with rapamycin. We found that certain mutations including pmc1Δ (Ca2+-ATPase), cps9-193 (small GTPase, Ryh1) and cps1-12 (1,3-β-d-glucan synthase, Bgs1) confer a rapamycin-sensitive phenotype to cells under salt stress with potassium chloride (>0.5 M). Cytometric analysis revealed that the mutant cells were unable to enter the mitotic cell cycle when treated with the drug under salt stress. Gene cloning and overexpression experiments revealed that the sensitivity to rapamycin was suppressed by the ectopic expression of tyrosine phosphatases, Pyp1 and Pyp2, which are negative regulators of Spc1/Sty1 mitogen-activated protein kinase (MAPK). The level of tyrosine phosphorylation on Spc1 was higher and sustained substantially longer in these mutants than in the wild type under salt stress. The hyperphosphorylation was significantly suppressed by overexpression of pyp1 + with concomitant resumption of the mutant cells’ growth. In fission yeast, TOR signaling has been thought to stimulate the stress-response pathway, because mutations of TORC2 components such as Tor1, Sin1 and Ste20 result in similar sensitive phenotypes to environmental stress. The present study, however, strongly suggests that TOR signaling is required for the down-regulation of a hyperactivated Spc1 for reentry into the mitotic cell cycle. This finding may shed light on our understanding of a new stress-responsive mechanism in TOR signaling in higher organisms. 相似文献
46.
Yu-Tao Xiang Robert W. Buchanan Gabor S. Ungvari Helen F. K. Chiu Kelly Y. C. Lai You-Hong Li Tian-Mei Si Chuan-Yue Wang Edwin H. M. Lee Yan-Ling He Shu-Yu Yang Mian-Yoon Chong Ee-Heok Kua Senta Fujii Kang Sim Michael K. H. Yong Jitendra K. Trivedi Eun-Kee Chung Pichet Udomratn Kok-Yoon Chee Norman Sartorius Chay-Hoon Tan Naotaka Shinfuku 《PloS one》2013,8(6)
47.
48.
Taeko Kimura Koji Tsutsumi Masato Taoka Taro Saito Masami Masuda-Suzukake Koichi Ishiguro Florian Plattner Takafumi Uchida Toshiaki Isobe Masato Hasegawa Shin-ichi Hisanaga 《The Journal of biological chemistry》2013,288(11):7968-7977
Neurodegenerative diseases associated with the pathological aggregation of microtubule-associated protein Tau are classified as tauopathies. Alzheimer disease, the most common tauopathy, is characterized by neurofibrillary tangles that are mainly composed of abnormally phosphorylated Tau. Similar hyperphosphorylated Tau lesions are found in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) that is induced by mutations within the tau gene. To further understand the etiology of tauopathies, it will be important to elucidate the mechanism underlying Tau hyperphosphorylation. Tau phosphorylation occurs mainly at proline-directed Ser/Thr sites, which are targeted by protein kinases such as GSK3β and Cdk5. We reported previously that dephosphorylation of Tau at Cdk5-mediated sites was enhanced by Pin1, a peptidyl-prolyl isomerase that stimulates dephosphorylation at proline-directed sites by protein phosphatase 2A. Pin1 deficiency is suggested to cause Tau hyperphosphorylation in Alzheimer disease. Up to the present, Pin1 binding was only shown for two Tau phosphorylation sites (Thr-212 and Thr-231) despite the presence of many more hyperphosphorylated sites. Here, we analyzed the interaction of Pin1 with Tau phosphorylated by Cdk5-p25 using a GST pulldown assay and Biacore approach. We found that Pin1 binds and stimulates dephosphorylation of Tau at all Cdk5-mediated sites (Ser-202, Thr-205, Ser-235, and Ser-404). Furthermore, FTDP-17 mutant Tau (P301L or R406W) showed slightly weaker Pin1 binding than non-mutated Tau, suggesting that FTDP-17 mutations induce hyperphosphorylation by reducing the interaction between Pin1 and Tau. Together, these results indicate that Pin1 is generally involved in the regulation of Tau hyperphosphorylation and hence the etiology of tauopathies. 相似文献
49.
Masanori Terai Naotaka Izumiyama-Shimomura Junko Aida Naoshi Ishikawa Mie Kuroiwa Steven S.S. Poon Tomio Arai Masashi Toyoda Hidenori Akutsu Akihiro Umezawa Ken-ichi Nakamura Kaiyo Takubo 《Tissue & cell》2013,45(6):407-413
Here we attempted to clarify telomere metabolism in parental cells and their derived clonal human induced pluripotent stem cells (iPSCs) at different passages using quantitative fluorescence in situ hybridization (Q-FISH). Our methodology involved estimation of the individual telomere lengths of chromosomal arms in individual cells within each clone in relation to telomere fluorescence units (TFUs) determined by Q-FISH. TFUs were very variable within the same metaphase spread and within the same cell. TFUs of the established iPSCs derived from human amnion (hAM933 iPSCs), expressed as mean values of the median TFUs of 20 karyotypes, were significantly longer than those of the parental cells, although the telomere extension rates varied quite significantly among the clones. Twenty metaphase spreads from hAM933 iPSCs demonstrated no chromosomal instability. The iPSCs established from fetal lung fibroblasts (MRC-5) did not exhibit telomere shortening and chromosomal instability as the number of passages increased. However, the telomeres of other iPSCs derived from MRC-5 became shorter as the number of passages increased, and one (5%) of 20 metaphase spreads showed chromosomal abnormalities including X trisomy at an early stage and all 20 showed abnormalities including X and 12 trisomies at the late stage. 相似文献
50.
Takaaki Kubota Yuichiro Ishiguro Azusa Takahashi-Nakaguchi Jane Fromont Tohru Gonoi Jun’ichi Kobayashi 《Bioorganic & medicinal chemistry letters》2013,23(1):244-247
Three new polyketides, manzamenones L–N (1–3), have been isolated from an Okinawan marine sponge of the genus Plakortis. The structures of 1–3 were elucidated on the basis of spectroscopic data. Manzamenones L–N (1–3) were new dimeric fatty-acid derivatives consisting of a tetrahydroindenone with three carboxy groups and two hexadecanyl chains. Manzamenones M (2) and N (3) showed antimicrobial activity against several bacteria and fungi. 相似文献