全文获取类型
收费全文 | 862532篇 |
免费 | 181816篇 |
国内免费 | 29900篇 |
出版年
2018年 | 10769篇 |
2017年 | 10102篇 |
2016年 | 13175篇 |
2015年 | 16239篇 |
2014年 | 18970篇 |
2013年 | 26171篇 |
2012年 | 29369篇 |
2011年 | 30509篇 |
2010年 | 22835篇 |
2009年 | 25587篇 |
2008年 | 28224篇 |
2007年 | 28962篇 |
2006年 | 26293篇 |
2005年 | 25414篇 |
2004年 | 25141篇 |
2003年 | 23871篇 |
2002年 | 24004篇 |
2001年 | 38358篇 |
2000年 | 35944篇 |
1999年 | 32836篇 |
1998年 | 16958篇 |
1997年 | 16602篇 |
1996年 | 15545篇 |
1995年 | 15169篇 |
1994年 | 14403篇 |
1993年 | 14086篇 |
1992年 | 27717篇 |
1991年 | 27295篇 |
1990年 | 27323篇 |
1989年 | 26260篇 |
1988年 | 24089篇 |
1987年 | 22659篇 |
1986年 | 21116篇 |
1985年 | 20645篇 |
1984年 | 16837篇 |
1983年 | 14531篇 |
1982年 | 11867篇 |
1981年 | 10698篇 |
1980年 | 10060篇 |
1979年 | 15377篇 |
1978年 | 12368篇 |
1977年 | 11346篇 |
1976年 | 10818篇 |
1975年 | 11532篇 |
1974年 | 12533篇 |
1973年 | 12309篇 |
1972年 | 11604篇 |
1971年 | 10464篇 |
1970年 | 9196篇 |
1969年 | 9088篇 |
排序方式: 共有10000条查询结果,搜索用时 28 毫秒
431.
432.
433.
Monitoring signal transduction in cancer: cDNA microarray for semiquantitative analysis. 总被引:1,自引:0,他引:1
H B Hsieh R A Lersch D E Callahan S Hayward M Wong O H Clark H U Weier 《The journal of histochemistry and cytochemistry》2001,49(8):1057-1058
This study targeted the development of a novel microarray tool to allow rapid determination of the expression levels of 58 different tyrosine kinase (tk) genes in small tumor samples. The goals were to define a reference probe for multi-sample comparison and to investigate the variability and reproducibility of the image acquisition and RT-PCR procedures. The small number of tk genes on our arrays enabled us to define a reference probe by artificially mixing all genes on the arrays. Such a probe provided contrast reference for comparative hybridization of control and sample DNA and enabled cross-comparison of more than two samples against one another. Comparison of signals generated from multiple scanning eliminated the concern of photo bleaching and scanner intrinsic noise. Tests performed with breast, thyroid, and prostate cancer samples yielded distinctive patterns and suggest the feasibility of our approach. Repeated experiments indicated reproducibility of such arrays. Up- or downregulated genes identified by this rapid screening are now being investigated with techniques such as in situ hybridization. 相似文献
434.
Shailesh Kumar Atma P. Dwivedi Vivek Kr. Kashyap A.K. Saxena A.K. Dwivedi Ranjana Srivastava Devi P. Sahu 《Bioorganic & medicinal chemistry letters》2013,23(8):2404-2407
Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log10 reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition. 相似文献
435.
S. Wehmeier A. S. Varghese S. S. Gurcha B. Tissot M. Panico P. Hitchen H. R. Morris G. S. Besra A. Dell M. C. M. Smith 《Molecular microbiology》2009,71(2):421-433
Previously mutations in a putative protein O -mannosyltransferase (SCO3154, Pmt) and a polyprenol phosphate mannose synthase (SCO1423, Ppm1) were found to cause resistance to phage, φC31, in the antibiotic producing bacteria Streptomyces coelicolor A3(2). It was proposed that these two enzymes were part of a protein O-glycosylation pathway that was necessary for synthesis of the phage receptor. Here we provide the evidence that Pmt and Ppm1 are indeed both required for protein O-glycosylation. The phosphate binding protein PstS was found to be glycosylated with a trihexose in the S. coelicolor parent strain, J1929, but not in the pmt − derivative, DT1025. Ppm1 was necessary for the transfer of mannose to endogenous polyprenol phosphate in membrane preparations of S. coelicolor . A mutation in ppm1 that conferred an E218V substitution in Ppm1 abolished mannose transfer and glycosylation of PstS. Mass spectrometry analysis of extracted lipids showed the presence of a glycosylated polyprenol phosphate (PP) containing nine repeated isoprenyl units (C45 -PP). S. coelicolor membranes were also able to catalyse the transfer of mannose to peptides derived from PstS, indicating that these could be targets for Pmt in vivo . 相似文献
436.
Bugreev D. V. Sinitsyna O. I. Buneva V. N. Nevinsky G. A. 《Russian Journal of Bioorganic Chemistry》2003,29(3):249-261
Data on the interaction of DNA type I topoisomerases from the murine and human placenta cells with specific and nonspecific oligonucleotides of various structures and lengths are summarized. The relative contributions of various contacts between the enzymes and DNA that have previously been detected by X-ray analysis to the total affinity of the topoisomerases for DNA substrates are estimated. Factors that determine the differences in the enzyme interactions with specific and nonspecific single- and double-stranded DNAs are revealed. The results of the X-ray analysis of human DNA topoisomerase I are interpreted taking into account data on the comprehensive thermodynamic and kinetic analysis of the enzyme interaction with the specific and nonspecific DNAs. 相似文献
437.
The potential for and constraints on the evolution of compensatory ability in Asclepias syriaca 总被引:2,自引:0,他引:2
To investigate the potential for and constraints on the evolution of compensatory ability, we performed a greenhouse experiment
using Asclepias syriaca in which foliar damage and soil nutrient concentration were manipulated. Under low nutrient conditions, significant genetic
variation was detected for allocation patterns and for compensatory ability. Furthermore, resource allocation to storage was
positively, genetically correlated both with compensatory ability and biomass when damaged, the last two being positively,
genetically correlated with each other. Thus, in the low nutrient environment, compensatory ability via resource allocation
to storage provided greater biomass when damaged. A negative genetic correlation between compensatory ability and plant biomass
when undamaged suggests that this mechanism entailed an allocation cost, which would constrain the evolution of greater compensatory
ability when nutrients are limited. Under high nutrient conditions, neither compensatory ability nor allocation patterns predicted
biomass when damaged, even though genetic variation in compensatory ability existed. Instead, plant biomass when undamaged
predicted biomass when damaged. The differences in outcomes between the two nutrient treatments highlight the importance of
considering the possible range of environmental conditions that a genotype may experience. Furthermore, traits that conferred
compensatory ability did not necessarily contribute to biomass when damaged, demonstrating that it is critical to examine
both compensatory ability and biomass when damaged to determine whether selection by herbivores can favor the evolution of
increased compensation.
Received: 2 April 1999 / Accepted: 21 September 1999 相似文献
438.
In Drosophila, as in vertebrates, each muscle is a syncytium and arises from mesodermal cells by successive fusion. This requires cell-cell recognition, alignment, formation of prefusion complexes, followed by electron-dense plaques and membrane breakdown. Because muscle development in Drosophila is rapid and well-documented, it has been possible to identify several genes essential for fusion. Molecular analysis of two of these genes revealed the importance of cytoplasmic components. One of these, Myoblast city, is expressed in several tissues and is homologous to the mammalian protein DOCK180. Myoblast city is presumably involved in cell recognition and cell adhesion. Blown fuse, the second cytoplasmic component, is selectively expressed in the mesoderm and essential in order to proceed from the prefusion complex to electron-dense plaques at opposed membranes between adjacent myoblasts. The rolling stone gene is transiently expressed during myoblast fusion. The Rost protein is located in the membrane and thus might be a key component for cell recognition. The molecular characterization of further genes relevant for fusion such as singles bar and sticks and stones will help to elucidate the mechanism of myoblast fusion in Drosophila. 相似文献
439.
440.