全文获取类型
收费全文 | 135篇 |
免费 | 0篇 |
国内免费 | 4篇 |
专业分类
系统科学 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 68篇 |
研究方法 | 13篇 |
综合类 | 56篇 |
出版年
2018年 | 1篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 8篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 7篇 |
2005年 | 7篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1991年 | 3篇 |
1988年 | 2篇 |
1987年 | 8篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 6篇 |
1971年 | 4篇 |
1970年 | 1篇 |
1969年 | 4篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 3篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有139条查询结果,搜索用时 15 毫秒
81.
Lee JE Silhavy JL Zaki MS Schroth J Bielas SL Marsh SE Olvera J Brancati F Iannicelli M Ikegami K Schlossman AM Merriman B Attié-Bitach T Logan CV Glass IA Cluckey A Louie CM Lee JH Raynes HR Rapin I Castroviejo IP Setou M Barbot C Boltshauser E Nelson SF Hildebrandt F Johnson CA Doherty DA Valente EM Gleeson JG 《Nature genetics》2012,44(2):193-199
Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein. We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme. Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction. 相似文献
82.
Kubo M Hata J Ninomiya T Matsuda K Yonemoto K Nakano T Matsushita T Yamazaki K Ohnishi Y Saito S Kitazono T Ibayashi S Sueishi K Iida M Nakamura Y Kiyohara Y 《Nature genetics》2007,39(2):212-217
Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 x 10(-7), crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCeta was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction. 相似文献
83.
Bifidobacteria can protect from enteropathogenic infection through production of acetate 总被引:3,自引:0,他引:3
Fukuda S Toh H Hase K Oshima K Nakanishi Y Yoshimura K Tobe T Clarke JM Topping DL Suzuki T Taylor TD Itoh K Kikuchi J Morita H Hattori M Ohno H 《Nature》2011,469(7331):543-547
The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection. 相似文献
84.
85.
86.
D-myo-inositol-1,4,5-trisphosphate (InsP3) is a putative intracellular second messenger for the mobilization of Ca2+ from intracellular stores, in particular, the endoplasmic reticulum. Specific binding sites on the endoplasmic reticulum may participate in the InsP3-induced release of Ca2+ from the Ca2+ pool. To examine the specific binding sites on the endoplasmic reticulum, we synthesized an arylazide derivative of InsP3 for photoaffinity labelling; InsP3 coupled to p-azidobenzoic acid (InsP3-pAB) using N,N'-carbonyldiimidazole (CDI) was obtained at a 9-11% yield. Here, we report that InsP3-pAB, but not an arylazide derivative of inositol-1,4-bisphophate (Ins(1,4)P2), causes the irreversible inhibition of InsP3-induced release of Ca2+ in saponin-permeabilized photo-irradiated macrophages. The irreversible inhibition by InsP3-pAB after photo-irradiation was prevented by a 10-fold excess of unmodified InsP3. 相似文献
87.
An alkaline hemoglobinolytic protease was extracted from the delayed hypersensitivity skin lesions induced by bovine gamma-globulin as an antigen in the guinea-pig. The enzyme was heat-labile and inhibited by thiol-blocking reagents. The mol.wt. was more than 100,000 and optimal pH around 9. 相似文献
88.
Two H,K-ATPase inhibitors and an inactive related compound have been isolated from a marine sponge Epipolasis sp. They are aromatic sesquiterpene alpha-curcumenes. 相似文献
89.
Y. Kitaura H. Takeno M. Aratani S. Okada S. Yonishi K. Hemmi O. Nakaguchi M. Hashimoto 《Cellular and molecular life sciences : CMLS》1982,38(9):1101-1103
Summary The bacterial cell-wall peptidoglycan peptides and related compounds coupled with some fatty acids were synthesized, and their immunostimulating property was examined by carbon clearance assay. All the new compounds (2–6) proved to possess significant potencies superior to that of FK-156 (1).Acknowledgment. We are grateful to Dr J. Mori and his coworkers for the biological assays. 相似文献
90.