全文获取类型
收费全文 | 225篇 |
免费 | 23篇 |
出版年
2021年 | 3篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 14篇 |
2012年 | 4篇 |
2011年 | 8篇 |
2010年 | 4篇 |
2009年 | 10篇 |
2008年 | 5篇 |
2007年 | 15篇 |
2006年 | 9篇 |
2005年 | 7篇 |
2004年 | 17篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 10篇 |
1998年 | 12篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1976年 | 2篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1966年 | 3篇 |
1954年 | 1篇 |
1953年 | 2篇 |
1952年 | 1篇 |
1946年 | 1篇 |
1942年 | 1篇 |
1940年 | 1篇 |
1938年 | 2篇 |
1926年 | 1篇 |
1919年 | 1篇 |
1905年 | 1篇 |
排序方式: 共有248条查询结果,搜索用时 834 毫秒
91.
DNA damage initiates a series of p53 pulses. Although much is known about the interactions surrounding p53, little is known about which interactions contribute to p53's dynamical behavior. The simplest explanation is that these pulses are oscillations intrinsic to the p53/Mdm2 negative feedback loop. Here we present evidence that this simple mechanism is insufficient to explain p53 pulses; we show that p53 pulses are externally driven by pulses in the upstream signaling kinases, ATM and Chk2, and that the negative feedback between p53 and ATM, via Wip1, is essential for maintaining the uniform shape of p53 pulses. We propose that p53 pulses result from repeated initiation by ATM, which is reactivated by persistent DNA damage. Our study emphasizes the importance of collecting quantitative dynamic information at high temporal resolution for understanding the regulation of signaling pathways and opens new ways to manipulate p53 pulses to ask questions about their function in response to DNA damage. 相似文献
92.
93.
We have computed the total energy as a function of six important torsion angles of the carcinogen N-2-acetylaminofluorene (AAF) bonded to thenitrogen N2 of deoxyguanosine using the semiempirical quantum mechanical method AM1. One global minimum and one local minimum are found separated by a modest barrier. We have computed the normal-mode frequencies of the relevant torsional motions and have determined the rate of conversion betweenthe two minima. 相似文献
94.
95.
96.
97.
98.
Forbidden synonymous substitutions in coding regions 总被引:2,自引:0,他引:2
In the evolution of highly conserved genes, a few "synonymous"
substitutions at third bases that would not alter the protein sequence are
forbidden or very rare, presumably as a result of functional requirements
of the gene or the messenger RNA. Another 10% or 20% of codons are
significantly less variable by synonymous substitution than are the
majority of codons. The changes that occur at the majority of third bases
are subject to codon usage restrictions. These usage restrictions control
sequence similarities between very distant genes. For example, 70% of third
bases are identical in calmodulin genes of man and trypanosome. Third-base
similarities of distant genes for conserved proteins are mathematically
predicted, on the basis of the G+C composition of third bases. These
observations indicate the need for reexamination of methods used to
calculate synonymous substitutions.
相似文献
99.
Human alpha-galactosidase A (alpha-Gal A) is the lysosomal glycohydrolase
that cleaves the terminal alpha-galactosyl moieties of various
glycoconjugates. Overexpression of the enzyme in Chinese hamster ovary
(CHO) cells results in high intracellular enzyme accumulation and the
selective secretion of active enzyme. Structural analysis of the N -linked
oligosaccharides of the intracellular and secreted glycoforms revealed that
the secreted enzyme's oligosaccharides were remarkably heterogeneous,
having high mannose (63%), complex (30%), and hybrid (5%) structures. The
major high mannose oligosaccharides were Man5-7GlcNAc2 species.
Approximately 40% of the high mannose and 30% of the hybrid
oligosaccharides had phosphate monoester groups. The complex
oligosaccharides were mono-, bi- , 2,4-tri-, 2,6-tri- and tetraantennary
with or without core-region fucose, many of which had incomplete outer
chains. Approximately 30% of the complex oligosaccharides were mono- or
disialylated. Sialic acids were mostly N -acetylneuraminic acid and
occurred exclusively in alpha2, 3-linkage. In contrast, the intracellular
enzyme had only small amounts of complex chains (7.7%) and had
predominantly high mannose oligosaccharides (92%), mostly Man5GlcNAc2 and
smaller species, of which only 3% were phosphorylated. The complex
oligosaccharides were fucosylated and had the same antennary structures as
the secreted enzyme. Although most had mature outer chains, none were
sialylated. Thus, the overexpression of human alpha-Gal A in CHO cells
resulted in different oligosaccharide structures on the secreted and
intracellular glycoforms, the highly heterogeneous secreted forms
presumably due to the high level expression and impaired glycosylation in
the trans- Golgi network, and the predominately Man5-7GlcNAc2 cellular
glycoforms resulting from carbohydrate trimming in the lysosome.
相似文献
100.