全文获取类型
收费全文 | 2506篇 |
免费 | 352篇 |
国内免费 | 4篇 |
出版年
2021年 | 36篇 |
2019年 | 24篇 |
2018年 | 27篇 |
2016年 | 54篇 |
2015年 | 83篇 |
2014年 | 98篇 |
2013年 | 98篇 |
2012年 | 123篇 |
2011年 | 111篇 |
2010年 | 70篇 |
2009年 | 67篇 |
2008年 | 89篇 |
2007年 | 103篇 |
2006年 | 82篇 |
2005年 | 98篇 |
2004年 | 90篇 |
2003年 | 85篇 |
2002年 | 71篇 |
2001年 | 81篇 |
2000年 | 61篇 |
1999年 | 73篇 |
1998年 | 32篇 |
1997年 | 26篇 |
1996年 | 30篇 |
1995年 | 26篇 |
1994年 | 28篇 |
1993年 | 27篇 |
1992年 | 54篇 |
1991年 | 49篇 |
1990年 | 52篇 |
1989年 | 47篇 |
1988年 | 42篇 |
1987年 | 38篇 |
1986年 | 39篇 |
1985年 | 45篇 |
1984年 | 35篇 |
1983年 | 37篇 |
1982年 | 25篇 |
1981年 | 24篇 |
1980年 | 24篇 |
1979年 | 39篇 |
1978年 | 29篇 |
1977年 | 30篇 |
1976年 | 31篇 |
1975年 | 22篇 |
1974年 | 33篇 |
1973年 | 33篇 |
1972年 | 29篇 |
1971年 | 35篇 |
1966年 | 32篇 |
排序方式: 共有2862条查询结果,搜索用时 15 毫秒
81.
Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase. 总被引:36,自引:21,他引:15 下载免费PDF全文
The serine/threonine kinase activity of the Raf-1 proto-oncogene product is stimulated by the activation of many tyrosine kinases, including growth factor receptors and pp60v-src. Recent studies of growth factor signal transduction pathways demonstrate that Raf-1 functions downstream of activated tyrosine kinases and p21ras and upstream of mitogen-activated protein kinase. However, coexpression of both activated tyrosine kinases and p21ras is required for maximal activation of Raf-1 in the baculovirus-Sf9 expression system. In this study, we investigated the role of tyrosine kinases and tyrosine phosphorylation in the regulation of Raf-1 activity. Using the baculovirus-Sf9 expression system, we identified Tyr-340 and Tyr-341 as the major tyrosine phosphorylation sites of Raf-1 when coexpressed with activated tyrosine kinases. Introduction of a negatively charged residue that may mimic the effect of phosphorylation at these sites activated the catalytic activity of Raf-1 and generated proteins that could transform BALB/3T3 cells and induce the meiotic maturation of Xenopus oocytes. In contrast, substitution of noncharged residues that were unable to be phosphorylated produced a protein that could not be enzymatically activated by tyrosine kinases and that could block the meiotic maturation of oocytes induced by components of the receptor tyrosine kinase pathway. These findings demonstrate that maturation of the tyrosine phosphorylation sites can dramatically alter the function of Raf-1. In addition, this is the first report that a transforming Raf-1 protein can be generated by a single amino acid substitution. 相似文献
82.
Margo T. Murphy Norma Morrison John S. Miles Robin H. Fraser Nigel K. Spurr Elizabeth Boyd 《Human genetics》1993,91(6):585-588
The gene encoding the Kell blood group polypeptide has been localized to chromosome 7q33-35 by in situ hybridization using a biotinylated 1.1-kb DNA fragment containing the 3 half of the human cDNA. This assignment is in accord with genetic localization using antigenic variation as a marker, and strongly suggests that Kell antigenic determinants are part of the polypeptide chain rather than the associated sugar molecules. 相似文献
83.
We studied the frequency of an SstI polymorphism in 70 patients with chronic B-cell leukaemia (CLL) and 100 normal controls. There was a highly significant difference in the distribution of the three genotypes between the CLL patients and the normal controls (2= 13.46, 2 df, P<0.001). The C2 allele was found more frequently in CLL patients and may be a marker for a predisposition to develop CLL. 相似文献
84.
Two novel microsatellite markers for prenatal prediction of spinal muscular atrophy (SMA) 总被引:1,自引:0,他引:1
K. E. Morrison R. J. Daniels G. K. Suthers G. A. Flynn M. J. Francis P. K. Grewal C. Dennis V. Buckle J. Ignatius V. Dubowitz K. E. Davies 《Human genetics》1993,92(2):133-138
Autosomal recessive spinal muscular atrophy (SMA) has been mapped to a 6-cM interval on chromosome 5q12–13.3, flanked proximally by locus D5S6 and distally by locus D5S112. In this study we describe the isolation of two new microsatellite markers (EF1/2a and EF13/14) near locus D5S125, which lies 2 cM distal to D5S6. We show by linkage analysis and the study of the recombinants in 55 SMA pedigrees that the disease lies in the 4-cM interval between EF1/2a and D5S112. Fluorescence in situ analysis of cosmids from D5S6, EF1/2a and D5S112 confirms the genetic order and relative distance of markers. The microsatellites EF1/2a and EF13/14 are the first highly polymorphic PCR based proximal markers in SMA to be described, and will be of value in prental prediction of the disorder. 相似文献
85.
Simona Picardi Briana Abrahms Emily Gelzer Thomas A. Morrison Tana Verzuh Jerod A. Merkle 《Ecology letters》2023,26(1):157-169
Site fidelity—the tendency to return to previously visited locations—is widespread across taxa. Returns may be driven by several mechanisms, including memory, habitat selection, or chance; however, pattern-based definitions group different generating mechanisms under the same label of ‘site fidelity’, often assuming memory as the main driver. We propose an operational definition of site fidelity as patterns of return that deviate from a null expectation derived from a memory-free movement model. First, using agent-based simulations, we show that without memory, intrinsic movement characteristics and extrinsic landscape characteristics are key determinants of return patterns and that even random movements may generate substantial probabilities of return. Second, we illustrate how to implement our framework empirically to establish ecologically meaningful, system-specific null expectations for site fidelity. Our approach provides a conceptual and operational framework to test hypotheses on site fidelity across systems and scales. 相似文献
86.
Male zebra finches normally learn their song from adult models during a restricted period of juvenile development. If song models are not available then, juveniles develop an isolate song which can be modified in adulthood. In this report we investigate the features of juvenile experience that underly the timing of song learning. Juvenile males raised in soundproof chambers or in visual isolation from conspecifics developed stable isolate song. However, whereas visual isolate song notes were similar to those of colony-reared males, soundproof chamber isolates included many phonologically abnormal notes in their songs. Despite having stable isolate songs, both groups copied new notes from tutors presented to them in adulthood (2.7 notes per bird for soundproof chamber isolates, 4.4 notes per bird for visual isolates). Old notes were often modified or eliminated. We infer that social interactions with live tutors are normally important for closing the sensitive period for song learning. Lesions of a forebrain nucleus (IMAN) had previously been shown to disrupt juvenile song learning, but not maintenance of adult song for up to 5 weeks after surgery. In this study, colony-reared adult males given bilateral lesions of IMAN retained all their song notes for up to 4–7.5 months after lesioning. However, similar lesions blocked all song note acquisition in adulthood by both visual and soundproof chamber isolates. Other work has shown that intact hearing is necessary for the maintenance of adult zebra finch song. We infer that auditory pathways used for song maintenance and acquisition differ: IMAN is necessary for auditorily guided song acquisition—whether by juveniles or adults—but not for adult auditorily guided song maintenance. © 1993 John Wiley & Sons, Inc. 相似文献
87.
Competence pheromone, oligopeptide permease, and induction of competence in Streptococcus pneumoniae 总被引:5,自引:4,他引:1
Geneviève Alioing Chantal Granadel Donald A. Morrison Jean-Pierre Claverys 《Molecular microbiology》1996,21(3):471-478
An unmodified heptadecapeptide pheromone capable of eliciting competence for genetic transformation in Streptococcus pneumoniae has recently been identified and characterized. In considering possible signaltransduction mechanisms for the peptide, the previously characterized Ami oligopeptide permease and the three highly homologous oligopeptide-binding lipoproteins, AmiA. AliA, and AliB, appeared to be good candidates for receptors. We therefore compared the spontaneous transformability of Ami, AliA and AliB mutants to that of an isogenic wild-type strain and we investigated the response of the various mutants to treatment with synthetic competence-stimulating peptide (CSP). Our results clearly demonstrate that neither Ami nor any of the three highly homologous oligopeptide-binding lipoproteins identified so far in S. pneumoniae are required for competence induction following treatment with synthetic CSP. Although the existence of a fourth unidentified oligopeptide-binding lipoprotein and/or a second oligopeptide permease operon could not be completely ruled out, we favour the hypothesis that CSP signal transmission rather involves a two-component regulatory system. Although none of the single or double Ami and Ali mutants tested appeared severely affected for competence, an exceptional aliB plasmid-insertion mutation abolished competence completely. In addition, the triple AmiA-AliA-AliB mutant differed from wild type in showing no sharp peak of competence but exhibiting transformability throughout the exponential phase of growth. These and previous observations are discussed and a general hypothesis is proposed to account for the modulation of competence by peptide permease mutants in S. pneumoniae. 相似文献
88.
89.
Lesley D. Morrison Laurence Becker †Lee C. Ang Stephen J. Kish 《Journal of neurochemistry》1995,65(2):636-642
Abstract: Depolarization of adult rat forebrain slices with veratrine induced the release of excitatory amino acids (glutamate and aspartate), the synthesis of nitric oxide (NO), and increases in cyclic GMP (cGMP). The NO synthase inhibitors N ω -monomethyl- l -arginine and N ω -nitro- l -arginine methyl ester decreased the release of NO and the levels of cGMP without affecting the release of excitatory amino acids. In contrast, the antiepileptic drug lamotrigine inhibited the release of excitatory amino acids and of NO, and decreased the levels of cGMP without causing a significant direct inhibition of the NO synthase. Furthermore, the synthesis of NO and the increases in cGMP induced by veratrine were partially blocked by the N -methyl- d -aspartate (NMDA) receptor antagonist MK-801 but not by 6-nitro-7-sulphamobenzo( f )quinoxaline-2,3-dione, a non-NMDA receptor antagonist. Neither of these compounds inhibited directly the NO synthase or the release of excitatory amino acids. Thus, these three types of compound act as an inhibitor of voltage-sensitive sodium channels (lamotrigine), as a receptor antagonist (MK-801), or as direct inhibitors of the NO synthase, to block the pathway leading to increased cGMP after veratrine depolarization. It is likely that some of the pharmacological and therapeutic actions shared by these three types of compound are, at least in part, a consequence of inhibition of the synthesis of NO. 相似文献
90.
Robert J. Belland S. G. Morrison John H. Carlson & Daniel M. Hogan 《Molecular microbiology》1997,23(1):123-135