全文获取类型
收费全文 | 431篇 |
免费 | 73篇 |
国内免费 | 1篇 |
专业分类
505篇 |
出版年
2023年 | 2篇 |
2021年 | 12篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 11篇 |
2016年 | 20篇 |
2015年 | 20篇 |
2014年 | 17篇 |
2013年 | 22篇 |
2012年 | 33篇 |
2011年 | 21篇 |
2010年 | 21篇 |
2009年 | 18篇 |
2008年 | 25篇 |
2007年 | 16篇 |
2006年 | 12篇 |
2005年 | 16篇 |
2004年 | 9篇 |
2003年 | 15篇 |
2002年 | 9篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 6篇 |
1998年 | 17篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 3篇 |
1978年 | 7篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1972年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有505条查询结果,搜索用时 0 毫秒
1.
2.
Transforming mutant v-mos protein kinases that are deficient in in vitro autophosphorylation. 总被引:4,自引:2,他引:2 下载免费PDF全文
We investigated the importance of specific serine residues for autophosphorylation and transformation by serine-threonine protein kinase p37mos. When either serine 326 or 358 was replaced with alanine, the resulting mutant protein retained the ability to transform NIH 3T3 cells but failed to autophosphorylate in vitro. These studies represent the first functional uncoupling of these two activities for p37mos. 相似文献
3.
Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. 总被引:26,自引:1,他引:25 下载免费PDF全文
Achondroplasia, the most common genetic form of dwarfism, is an autosomal dominant disorder whose underlying mechanism is a defect in the maturation of the cartilage growth plate of long bones. Achondroplasia has recently been shown to result from a Gly to Arg substitution in the transmembrane domain of the fibroblast growth factor receptor 3 (FGFR3), although the molecular consequences of this mutation have not been investigated. By substituting the transmembrane domain of the Neu receptor tyrosine kinase with the transmembrane domains of wild-type and mutant FGFR3, the Arg380 mutation in FGFR3 is shown to activate both the kinase and transforming activities of this chimeric receptor. Residues with side chains capable of participating in hydrogen bond formation, including Glu, Asp, and to a lesser extent, Gln, His and Lys, were able to substitute for the activating Arg380 mutation. The Arg380 point mutation also causes ligand-independent stimulation of the tyrosine kinase activity of FGFR3 itself, and greatly increased constitutive levels of phosphotyrosine on the receptor. These results suggest that the molecular basis of achondroplasia is unregulated signal transduction through FGFR3, which may result in inappropriate cartilage growth plate differentiation and thus abnormal long bone development. Achondroplasia may be one of the number of cogenital disorders where constitutive activation of a member of the FGFR family leads to development abnormalities. 相似文献
4.
Martin F. Wojciechowski Michael J. Sanderson Bruce G. Baldwin Michael J. Donoghue 《American journal of botany》1993,80(6):711-722
Evolutionary relationships within Astragalus L. (Fabaceae) were inferred from nucleotide sequence variation in nuclear ribosomal DNA of both New World and Old World species. The internal transcribed spacer regions (ITS) of 18S–26S nuclear ribosomal DNA from representatives of 26 species of Astragalus, three species of Oxytropis DC., and two outgroup taxa were analyzed by polymerase chain reaction amplification and direct DNA sequencing. The length of the ITS 1 region within these taxa varied from 221 to 231 bp, while ITS 2 varied in length from 207 to 217 bp. Of the aligned, unambiguous positions, approximately 34% were variable in each spacer region. In pairwise comparisons among Astragalus species and outgroup taxa, sequence divergence at these sites ranged from 0 to 18.8% in ITS 1 and from 0 to 21.7% in ITS 2. Parsimony analyses of these sequences resulted in a well-resolved phylogeny that is highly concordant with previous cytogenetic and chloroplast DNA evidence for a major phylogenetic division in the genus. These data suggest that the New World aneuploid species of Astragalus form a monophyletic but morphologically cryptic group derived from euploid species of Old World (Eurasian) origin, which are consequently paraphyletic. 相似文献
5.
6.
A phage-plasmid hybrid was constructed for use as a recombinant DNA vector, allowing the propagation of cloned EcoRI restriction endonuclease fragments of about 2 X 10(6) to 11 X 10(6) daltons. The colicin E1 plasmid replicon was fused to the left arm of a lambdagt generalized transducing phage with a thermolabile repressor, yielding a genome which could be replicated either by phage lambda functions or via the colicin E1 plasmid replicon. At the nonpermissive temperature, phage functions were derepressed and phage growth occurred lytically. Alternatively, at the permissive temperature, lambda functions were repressed and the vector replicated as a covalently closed circular plasmid. The phage-plasmid hybrid vector could be maintained at a copy number determined by the colicin E1 plasmid replicon and was also sensitive to amplification after chloramphenicol treatment. An EcoRI fragment of Escherichia coli DNA encoding genes of the arabinose operon also was inserted into the central portion of the vector. 相似文献
7.
8.
Membrane-anchored form of v-sis/PDGF-B induces mitogenesis without detectable PDGF receptor autophosphorylation 总被引:5,自引:4,他引:1 下载免费PDF全文
The v-sis protein is structurally and functionally related to PDGF. Forms of the v-sis protein which are anchored to the cell membrane via the transmembrane domain of the vesicular stomatitis virus G protein have been previously described (Hannink, M., and D.J. Donoghue. 1986. J. Cell Biol. 103:2311-2322). Several of these fusion proteins were shown to interact productively with the PDGF receptor (PDGFR) based on their ability to transform NIH 3T3 cells. In this report, we further characterized one of these membrane-anchored v-sis proteins, designated v-sis239-G. The gene encoding v-sis239-G was placed under control of the Drosophila melanogaster hsp70 promotor and synthesis of this protein was shown to induce a mitogenic response in NIH 3T3 cells. Unexpectedly, v-sis239-G did not induce detectable autophosphorylation of the PDGFR, in contrast to a similarly expressed secreted form of the v-sis protein. Thus, it appears that a PDGFR-mediated mitogenic response may be dissociated from detectable receptor autophosphorylation. Furthermore, induced synthesis of v-sis239-G was shown to lead to c-fos expression even in the absence of detectable receptor autophosphorylation. Interestingly, a nonmitogenic membrane-anchored form of the v-sis protein, designated v-sis239-G338, also induced c-fos without receptor autophosphorylation. These results raise interesting questions regarding the roles of autophosphorylation and c-fos induction in PDGFR-mediated signal transduction and suggest the possibility of an autophosphorylation-independent signal transduction pathway. 相似文献
9.
Mammalian muscle cells bear a cell-autonomous, heritable memory of their rostrocaudal position. 总被引:6,自引:0,他引:6
We previously documented a greater than 100-fold rostrocaudal gradient of chloramphenicol acetyltransferase (CAT) expression in the muscles of adult mice that bear a myosin light chain-CAT transgene: successively more caudal muscles express successively higher levels of CAT. Here we studied the development and maintenance of this positional information in vitro. CAT levels reflect the rostrocaudal positions of the muscles from which the cells are derived in cultures established from adult muscles, in clones derived from individual adult myogenic (satellite) cells, in cultures prepared from embryonic myoblasts, and in cell lines derived by retrovirus-mediated transfer of an oncogene to satellite cells. Our results suggest that myoblasts bear a positional memory that is established in embryos, retained in adults, cell autonomous, heritable, stable to transformation, and accessible to study in clonal cell lines. 相似文献
10.
Park SH Hanning I Jarquin R Moore P Donoghue DJ Donoghue AM Ricke SC 《FEMS microbiology letters》2011,316(1):7-15
Three pathogens, Campylobacter, Salmonella, and Shiga-toxin-producing Escherichia coli, are leading causes of bacterial gastroenteritis in the United States and worldwide. Although these three bacteria are typically considered food-borne pathogens, outbreaks have been reported due to contaminated drinking water and irrigation water. The aim of this research was to develop two types of PCR assays that could detect and quantify three pathogens, Campylobacter spp., E. coli O157:H7, and Salmonella spp., in watershed samples. In conventional PCR, three target strains were detected by multiplex PCR (m-PCR) using each specific primer pair simultaneously. Under optimized m-PCR conditions, the assay produced a 90-bp product for Campylobacter jejuni, a 150-bp product for E. coli O157:H7, and a 262-bp product for Salmonella Typhimurium, and the limitation of detection was approximately 700 copies for all three bacteria. In addition, real-time PCR was performed to quantify the three pathogens using SYBR green fluorescence. The assay was designed so that each target had a different melting temperature [C. jejuni (80.1 °C), E. coli O157:H7 (83.3 °C), and S. Typhimurium (85.9 °C)]. Therefore, this system could quantify and distinguish three pathogens simultaneously in a single reaction. 相似文献