全文获取类型
收费全文 | 349篇 |
免费 | 31篇 |
出版年
2021年 | 5篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 18篇 |
2013年 | 15篇 |
2012年 | 23篇 |
2011年 | 16篇 |
2010年 | 22篇 |
2009年 | 11篇 |
2008年 | 12篇 |
2007年 | 16篇 |
2006年 | 12篇 |
2005年 | 7篇 |
2004年 | 6篇 |
2003年 | 18篇 |
2002年 | 13篇 |
2001年 | 5篇 |
2000年 | 11篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1964年 | 2篇 |
1959年 | 2篇 |
排序方式: 共有380条查询结果,搜索用时 15 毫秒
1.
Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 A resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain. 相似文献
2.
3.
Francis G. Spinale Rupak Mukherjee Juozas A. Zavadzkas Christine N. Koval Shenikqua Bouges Robert E. Stroud Lawrence W. Dobrucki Albert J. Sinusas 《The Journal of biological chemistry》2010,285(39):30316-30327
The membrane type-1 matrix metalloproteinase (MT1-MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 ± 2 versus 32 ± 2%,p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the post-MI MT1-MMPexp group. Early and persistent MT1-MMP promoter activity occurred post-MI, and increased myocardial MT1-MMP levels resulted in poor survival, worsening of LV function, and significant fibrosis. A molecular mechanism for the adverse LV matrix remodeling with MT1-MMP induction is increased processing of pro-fibrotic signaling molecules. Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling. 相似文献
4.
M R Stroud S B Levery M E Salyan C E Roberts S Hakomori 《European journal of biochemistry》1992,203(3):577-586
A Lewis-b-active glycosphingolipid containing a repetitive type-1 chain carbohydrate core was isolated from human colonic adenocarcinoma cell line Colo205. This glycosphingolipid was purified by HPLC and preparative high-performance thin-layer chromatography and its structure elucidated by positive-ion fast-atom-bombardment mass spectrometry with collision-induced disassociation, 1H-NMR spectroscopy and methylation analysis. The glycosphingolipid was found to be a trifucosylated derivative of this novel carbohydrate core, having the following structure: [formula; see text]. 相似文献
5.
Salt toxicosis in waterfowl in North Dakota 总被引:1,自引:0,他引:1
About 150 waterfowl died and another 250 became weak and lethargic from suspected salt poisoning after using White Lake, a highly saline lake in Mountrail County, North Dakota. Frigid temperatures made fresh water unavailable, forcing the birds to ingest the saline waters with resultant toxic effects. Sick birds recovered when removed from the salt water and released into fresh water marshes. Brain sodium levels were higher in dead geese submitted for necropsy than in controls. 相似文献
6.
7.
Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis. 总被引:24,自引:6,他引:18
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M E Basson M Thorsness J Finer-Moore R M Stroud J Rine 《Molecular and cellular biology》1988,8(9):3797-3808
The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis. 相似文献
8.
9.
Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex 总被引:14,自引:1,他引:13
Two regions of the genome, a 1-kbp portion of the zeste locus and a 1.1-
kbp portion of the yolk protein 2 locus, were sequenced in six individuals
from each of four species: Drosophila melanogaster, D. simulans, D.
mauritiana, and D. sechellia. The species and strains were the same as
those of a previous study of a 1.9-kbp region of the period locus. No
evidence was found for recent balancing or directional selection or for the
accumulation of selected differences between species. Yolk protein 2 has a
high level of amino acid replacement variation and a low level of
synonymous variation, while zeste has the opposite pattern. This contrast
is consistent with information on gene function and patterns of codon bias.
Polymorphism levels are consistent with a ranking of effective population
sizes, from low to high, in the following order: D. sechellia, D.
melanogaster, D.mauritiana, and D. simulans. The apparent species
relationships are very similar to those suggested by the period locus
study. In particular, D. simulans appears to be a large population that is
still segregating variation that arose before the separation of D.
mauritiana and D. sechellia. It is estimated that the separation of
ancestral D. melanogaster from the other species occurred 2.5-3.4 Mya. The
separations of D. sechellia and D. mauritiana from ancestral D. simulans
appear to have occurred 0.58- 0.86 Mya, with D. mauritiana having diverged
from ancestral D. simulans 0.1 Myr more recently than D. sechellia.
相似文献
10.