全文获取类型
收费全文 | 222篇 |
免费 | 90篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 6篇 |
2012年 | 6篇 |
2011年 | 2篇 |
2010年 | 3篇 |
2009年 | 11篇 |
2008年 | 13篇 |
2007年 | 6篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 12篇 |
2003年 | 7篇 |
2002年 | 11篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1971年 | 3篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1953年 | 1篇 |
1930年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有312条查询结果,搜索用时 15 毫秒
181.
Albert A. Dahlberg 《American journal of physical anthropology》1978,48(2):257-257
Exceptions have been cited which rule against the simple autosomal recessive hypothesis for the transmission of susceptibility to infection with Australia antigen (HBsAg). An attempt is made here to present a genetic model for a complex segregation analysis of a new and unique set of data to test this hypothesis. Regression techniques were used to estimate in four populations, age and sexspecific penetrance levels and the frequency of the gene whose product is hypothesized to be HBsAg. While the genetic hypothesis was not in general supported, observed deviations and their possible causes are discussed. 相似文献
182.
183.
184.
185.
Chaohong Liu Xiaoming Bai Junfeng Wu Shruti Sharma Arpita Upadhyaya Carin I. M. Dahlberg Lisa S. Westerberg Scott B. Snapper Xiaodong Zhao Wenxia Song 《PLoS biology》2013,11(11)
Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR) signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of signaling remains elusive. Using genetically manipulated mouse models and total internal reflection fluorescence microscopy, we demonstrate that neuronal Wiskott–Aldrich syndrome protein (N-WASP), which is coexpressed with WASP in all immune cells, is a critical negative regulator of B-cell signaling. B-cell–specific N-WASP gene deletion causes enhanced and prolonged BCR signaling and elevated levels of autoantibodies in the mouse serum. The increased signaling in N-WASP knockout B cells is concurrent with increased accumulation of F-actin at the B-cell surface, enhanced B-cell spreading on the antigen-presenting membrane, delayed B-cell contraction, inhibition in the merger of signaling active BCR microclusters into signaling inactive central clusters, and a blockage of BCR internalization. Upon BCR activation, WASP is activated first, followed by N-WASP in mouse and human primary B cells. The activation of N-WASP is suppressed by Bruton''s tyrosine kinase-induced WASP activation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibits WASP activation. Our results reveal a new mechanism for the negative regulation of BCR signaling and broadly suggest an actin-mediated mechanism for signaling down-regulation. 相似文献
186.
187.
188.
189.
190.
Capreomycin susceptibility is increased by TlyA-directed 2'-O-methylation on both ribosomal subunits
The binding site of the cyclic peptide antibiotics capreomycin and viomycin is located on the ribosomal subunit interface close to nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA. In Mycobacterium tuberculosis, the 2'-hydroxyls of both nucleotides are methylated by the enzyme TlyA. Loss of these methylations through inactivation of TlyA confers resistance to capreomycin and viomycin. We report here that TlyA orthologues occur in diverse bacteria and fall into two distinct groups. One group, now termed TlyA(I) , has shorter N- and C-termini and methylates only C1920; the second group (now TlyA(II) ) includes the mycobacterial enzyme, and these longer orthologues methylate at both C1409 and C1920. Ribosomal subunits are the preferred substrates for both groups of orthologues. Amino acid substitutions at the N-terminus of TlyA(II) reduce its ability to methylate these substrates. Growing pairs of recombinant TlyA(II) Escherichia coli strains in competition shows that even subtle changes in the level of rRNA methylation lead to significant differences in susceptibility to sub-inhibitory concentrations of capreomycin. The findings reveal that 2'-O-methyls at both C1409 and C1920 play a role in facilitating the inhibitory effects of capreomycin and viomycin on the bacterial ribosome. 相似文献