全文获取类型
收费全文 | 273篇 |
免费 | 36篇 |
国内免费 | 1篇 |
专业分类
310篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2019年 | 4篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 7篇 |
2014年 | 6篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 8篇 |
2009年 | 5篇 |
2008年 | 10篇 |
2007年 | 14篇 |
2006年 | 8篇 |
2005年 | 15篇 |
2004年 | 25篇 |
2003年 | 16篇 |
2002年 | 9篇 |
2001年 | 12篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1981年 | 5篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有310条查询结果,搜索用时 15 毫秒
41.
A previously uncharacterized yeast protein, YJL066c, was discovered in the membrane fraction although it has no hydrophobic stretch. The protein was partly solubilized by Triton X-100 in an oligomeric form, while it was insoluble in alkali or salt. By immunofluorescent microscopy, its localization coincided with the mitochondria. We therefore propose it should be named Mpm1 (mitochondrial peculiar membrane protein 1). 相似文献
42.
43.
44.
45.
Ohte S Shin M Sasanuma H Yoneyama K Akita M Ikebuchi K Jimi E Maruki Y Matsuoka M Namba A Tomoda H Okazaki Y Ohtake A Oda H Owan I Yoda T Furuya H Kamizono J Kitoh H Nakashima Y Susami T Haga N Komori T Katagiri T 《Biochemical and biophysical research communications》2011,(1):213-218
Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G0/G1 phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLCγ inhibitor, increased the proportion of cells in the G0/G1 phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G0/G1 phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation. 相似文献
46.
Vestergaard MC Yoda T Hamada T Akazawa Ogawa Y Yoshida Y Takagi M 《Biochimica et biophysica acta》2011,1808(9):2245-2251
The effect of temperature change(s) on the dynamics of giant unilamellar vesicles containing oxidized and non-oxidized cholesterol was investigated and characterized. We have demonstrated that (i) major cholesterol auto-oxidation products, 7β-hydroxycholesterol (7β) and 7-ketocholesterol (7keto), rendered vesicles more responsive to temperature changes; (ii) 7keto imparted greater thermo-induced membrane dynamics than 7β; (iii) 7β and 7keto vesicles synergistically were more thermo-responsive than the individual oxysterols; (iv) the thermo-responsiveness of 7keto-containing vesicles was equivalent to that of 25 hydroxycholesterol (25OH)-containing vesicles; and (v) we have characterized the observed membrane dynamics. The results provide a new plausible mechanism: oxidative-stressed membranes in conjunction with temperature change induce membrane dynamics. These findings improve the mechanisms reported previously that attributed the induced dynamics solely to membrane oxidation. 相似文献
47.
Furutani-Seiki M Sasado T Morinaga C Suwa H Niwa K Yoda H Deguchi T Hirose Y Yasuoka A Henrich T Watanabe T Iwanami N Kitagawa D Saito K Asaka S Osakada M Kunimatsu S Momoi A Elmasri H Winkler C Ramialison M Loosli F Quiring R Carl M Grabher C Winkler S Del Bene F Shinomiya A Kota Y Yamanaka T Okamoto Y Takahashi K Todo T Abe K Takahama Y Tanaka M Mitani H Katada T Nishina H Nakajima N Wittbrodt J Kondoh H 《Mechanisms of development》2004,121(7-8):647-658
A large-scale mutagenesis screen was performed in Medaka to identify genes acting in diverse developmental processes. Mutations were identified in homozygous F3 progeny derived from ENU-treated founder males. In addition to the morphological inspection of live embryos, other approaches were used to detect abnormalities in organogenesis and in specific cellular processes, including germ cell migration, nerve tract formation, sensory organ differentiation and DNA repair. Among 2031 embryonic lethal mutations identified, 312 causing defects in organogenesis were selected for further analyses. From these, 126 mutations were characterized genetically and assigned to 105 genes. The similarity of the development of Medaka and zebrafish facilitated the comparison of mutant phenotypes, which indicated that many mutations in Medaka cause unique phenotypes so far unrecorded in zebrafish. Even when mutations of the two fish species cause a similar phenotype such as one-eyed-pinhead or parachute, more genes were found in Medaka than in zebrafish that produced the same phenotype when mutated. These observations suggest that many Medaka mutants represent new genes and, therefore, are important complements to the collection of zebrafish mutants that have proven so valuable for exploring genomic function in development. 相似文献
48.
Yoda H Hirose Y Yasuoka A Sasado T Morinaga C Deguchi T Henrich T Iwanami N Watanabe T Osakada M Kunimatsu S Wittbrodt J Suwa H Niwa K Okamoto Y Yamanaka T Kondoh H Furutani-Seiki M 《Mechanisms of development》2004,121(7-8):715-728
We screened for mutations affecting retinotectal axonal projection in Medaka, Oryzias latipes. In wild-type Medaka embryos, all the axons of retinal ganglion cells (RGCs) project to the contralateral tectum, such that the topological relationship of the retinal field is maintained. We labeled RGC axons using DiI/DiO at the nasodorsal and temporoventral positions of the retina, and screened for mutations affecting the pattern of stereotypic projections to the tectum. By screening 184 mutagenized haploid genomes, seven mutations in five genes causing defects in axonal pathfinding were identified, whereas mutations affecting the topographic projection of RGC axons were not found. The mutants were grouped into two classes according to their phenotypes. In mutants of Class I, a subpopulation of the RGC axons branched out either immediately after leaving the eye or after reaching the midline, and this axonal subpopulation projected to the ipsilateral tectum. In mutants of Class II, subpopulations of RGC axons branched out after crossing the midline and projected aberrantly. These mutants will provide clues to understanding the functions of genes essential for axonal pathfinding, which may be conserved or partly divergent among vertebrates. 相似文献
49.
Sasado T Morinaga C Niwa K Shinomiya A Yasuoka A Suwa H Hirose Y Yoda H Henrich T Deguchi T Iwanami N Watanabe T Kunimatsu S Osakada M Okamoto Y Kota Y Yamanaka T Tanaka M Kondoh H Furutani-Seiki M 《Mechanisms of development》2004,121(7-8):817-828
The development of germ cells has been intensively studied in Medaka (Oryzias latipes). We have undertaken a large-scale screen to identify mutations affecting the development of primordial germ cells (PGCs) in Medaka. Embryos derived from mutagenized founder fish were screened for an abnormal distribution or number of PGCs at embryonic stage 27 by RNA in situ hybridization for the Medaka vasa homologue (olvas). At this stage, PGCs coalesce into two bilateral vasa-expressing foci in the ventrolateral regions of the trunk after their migration and group organization. Nineteen mutations were identified from a screen corresponding to 450 mutagenized haploid genomes. Eleven of the mutations caused altered PGC distribution. Most of these alterations were associated with morphological abnormalities and could be grouped into four phenotypic classes: Class 1, PGCs dispersed into bilateral lines; Class 2, PGCs dispersed in a region more medial than that in Class 1; Class 3, PGCs scattered laterally and over the yolk sac area; and Class 4, PGCs clustered in a single median focus. Eight mutations caused a decrease in the number of PGCs. This decrease was observed in the offspring of heterozygous mothers, indicating the contribution of a maternal factor in determining PGC abundance. Taken together, these mutations should prove useful in identifying molecular mechanisms underlying the early PGC development and migration. 相似文献
50.
Kitagawa D Watanabe T Saito K Asaka S Sasado T Morinaga C Suwa H Niwa K Yasuoka A Deguchi T Yoda H Hirose Y Henrich T Iwanami N Kunimatsu S Osakada M Winkler C Elmasri H Wittbrodt J Loosli F Quiring R Carl M Grabher C Winkler S Del Bene F Momoi A Katada T Nishina H Kondoh H Furutani-Seiki M 《Mechanisms of development》2004,121(7-8):673-685
The forebrain, consisting of the telencephalon and diencephalon, is essential for processing sensory information. To genetically dissect formation of the forebrain in vertebrates, we carried out a systematic screen for mutations affecting morphogenesis of the forebrain in Medaka. Thirty-three mutations defining 25 genes affecting the morphological development of the forebrain were grouped into two classes. Class 1 mutants commonly showing a decrease in forebrain size, were further divided into subclasses 1A to 1D. Class 1A mutation (1 gene) caused an early defect evidenced by the lack of bf1 expression, Class 1B mutations (6 genes) patterning defects revealed by the aberrant expression of regional marker genes, Class 1C mutation (1 gene) a defect in a later stage, and Class 1D (3 genes) a midline defect analogous to the zebrafish one-eyed pinhead mutation. Class 2 mutations caused morphological abnormalities in the forebrain without considerably affecting its size, Class 2A mutations (6 genes) caused abnormalities in the development of the ventricle, Class 2B mutations (2 genes) severely affected the anterior commissure, and Class 2C (6 genes) mutations resulted in a unique forebrain morphology. Many of these mutants showed the compromised sonic hedgehog expression in the zona-limitans-intrathalamica (zli), arguing for the importance of this structure as a secondary signaling center. These mutants should provide important clues to the elucidation of the molecular mechanisms underlying forebrain development, and shed new light on phylogenically conserved and divergent functions in the developmental process. 相似文献