全文获取类型
收费全文 | 18536篇 |
免费 | 924篇 |
国内免费 | 27篇 |
专业分类
19487篇 |
出版年
2024年 | 31篇 |
2023年 | 165篇 |
2022年 | 377篇 |
2021年 | 708篇 |
2020年 | 416篇 |
2019年 | 441篇 |
2018年 | 644篇 |
2017年 | 603篇 |
2016年 | 786篇 |
2015年 | 889篇 |
2014年 | 1131篇 |
2013年 | 1552篇 |
2012年 | 1638篇 |
2011年 | 1438篇 |
2010年 | 833篇 |
2009年 | 729篇 |
2008年 | 843篇 |
2007年 | 818篇 |
2006年 | 684篇 |
2005年 | 621篇 |
2004年 | 507篇 |
2003年 | 417篇 |
2002年 | 376篇 |
2001年 | 308篇 |
2000年 | 280篇 |
1999年 | 254篇 |
1998年 | 100篇 |
1997年 | 76篇 |
1996年 | 82篇 |
1995年 | 77篇 |
1994年 | 57篇 |
1993年 | 56篇 |
1992年 | 152篇 |
1991年 | 143篇 |
1990年 | 113篇 |
1989年 | 85篇 |
1988年 | 126篇 |
1987年 | 97篇 |
1986年 | 80篇 |
1985年 | 81篇 |
1984年 | 81篇 |
1983年 | 46篇 |
1982年 | 40篇 |
1981年 | 47篇 |
1980年 | 43篇 |
1979年 | 56篇 |
1978年 | 35篇 |
1977年 | 43篇 |
1976年 | 31篇 |
1974年 | 29篇 |
排序方式: 共有10000条查询结果,搜索用时 7 毫秒
921.
Tumorigenicity of EJ-ras oncogene transformed NIH 3T3 cells and expression of plasminogen activators
M K Sidhu M S Russo K A Zirvi L Scala S Kumar 《Cell biology international reports》1990,14(6):527-542
A number of clonal cell lines have been isolated from NIH 3T3 cells transfected with the plasmid, pSV2 gpt-EJ-ras. The plasmid expresses Val12 instead of Gly12 in p21 ras protein and can be selected for the expression of E. coli XGPRT gene in mammalian cells. Southern analyses of the Eco R1 and Bam H1 digests of chromosomal DNA shows that multiple copies of the plasmid are integrated in a tandem sequence in the clones used in this study. The transfectants showed refractile appearance and criss-crossed pattern of growth, exhibited elevated expression of ras mRNA and formed tumors in nude mice commensurate with the copy number of the integrated EJ-ras gene. The increased propensity to form tumors did not correlate with the expression of urinary or tissue plasminogen activators (u-PA or t-PA). The cellular and secreted activity of u-PA in fact decreased as the ras gene expression increased. These data show that the enhanced tumorigenicity of transformed murine cells is related to the tandem integration and expression of human EJ-ras. The overexpression of ras has very little effect on t-PA but appears to suppress u-PA activity. 相似文献
922.
The molecular mechanisms of toxicity associated with cytoplasmic accumulation of TAR DNA binding protein-43(TDP-43),a pathological feature of many neurodegenera... 相似文献
923.
924.
925.
Shearwin-Whyatt L Baliga B Doumanis J Kumar S 《Biochemical and biophysical research communications》2001,282(5):1114-1119
Cellular defects which prevent apoptotic cell death can result in the generation of hyperproliferative disorders and can prevent the effective treatment of such diseases. The majority of cellular defects which result in apoptosis resistance lie upstream of caspase activation. We have described chimeric caspase molecules consisting of the prodomain of caspase-2 fused to the amino terminus of caspase-3, and which are tagged at the carboxyl terminus with green fluorescent protein (GFP) to allow direct visualisation of transfected cells. Here we show that these chimeric caspase molecules possess potent, rapid cell-killing activity in cell lines which display a range of defects resulting in apoptosis resistance. 相似文献
926.
Combinatorial random mutageneses involving either Asn43 with Asn44 (set 1) or Glu46 with an adjacent insertion (set 2) were undertaken to explore the functional perfection of the guanine recognition loop of ribonuclease T(1) (RNase T(1)). Four hundred unique recombinants were screened in each set for their ability to enhance enzyme catalysis of RNA cleavage. After a thorough selection procedure, only six variants were found that were either as active or more active than wild type which included substitutions of Asn43 by Gly, His, Leu, or Thr, an unplanned Tyr45Ser substitution and Glu46Pro with an adjacent Glu47 insertion. Asn43His-RNase T(1) has the same loop sequence as that for RNases Pb(1) and Fl(2). None of the most active mutants were single substitutions at Asn44 or double substitutions at Asn43 and Asn44. A total of 13 variants were purified, and these were subjected to kinetic analysis using RNA, GpC, and ApC as substrates. Modestly enhanced activities with GpC and RNA involved both k(cat) and K(M) effects. Mutants having low activity with GpC had proportionately even lower relative activity with RNA. Asn43Gly-RNase T(1) and all five of the purified mutants in set 2 exhibited similar values of k(cat)/K(M) for ApC which were the highest observed and about 10-fold that for wild type. The specificity ratio [(k(cat)/K(M))(GpC)/(k(cat)/K(M))(ApC)] varied over 30 000-fold including a 10-fold increase [Asn43His variant; mainly due to a low (k(cat)/K(M))(ApC)] and a 3000-fold decrease (Glu46Ser/(insert)Gly47 variant; mainly due to a low (k(cat)/K(M))(GpC)) as compared with wild type. It is interesting that k(cat) (GpC) for the Tyr45Ser variant was almost 4-fold greater than for wild type and that Pro46/(insert)Glu47 RNase T(1) is 70-fold more active than the permuted variant (insert)Pro47-RNase T(1) which has a conserved Glu46. In any event, the observation that only 6 out of 800 variants surveyed had wild-type activity supports the view that functional perfection of the guanine recognition loop of RNase T(1) has been achieved. 相似文献
927.
Kumar SS Malladi V Sankaran K Haigh R Williams P Balakrishnan A 《Canadian journal of microbiology》2001,47(8):727-734
Enteropathogenic Escherichia coli (EPEC) causes persistent infantile diarrhoea. This nontoxigenic E. coli exhibits a complicated pathogenic mechanism in which its outer membrane proteins and type III secretory proteins damage intestinal epithelium and cause diarrhoea. In accordance with this, our previous study using HEp-2 cells demonstrated cytopathic effects caused by cell-free outer membrane preparations of EPEC. In this study, we report the extrusion of actin-positive strands from HEp-2 and Int 407 cells when treated with outer membrane preparations. An interesting observation of this work, perhaps relevant to the characteristic localized three-dimensional colony formation of EPEC, is the attachment of a wild type EPEC strain to these actin-positive strands. 相似文献
928.
Pattanayak D Chakrabarti SK Kumar PA Naik PS 《Indian journal of experimental biology》2001,39(9):897-901
RAPD based fingerprinting of 21 serovars of Bacillus thuringiensis (Bt) representing different serotypes was performed using 19 random decamer primers. A total of 172 polymorphic fragments, ranging in size from 161-2789 bp, were amplified from 13 of the 19 primers. Pairwise genetic similarity analysis revealed very low similarity values, ranging from 3-68%, among the serovars of Bt, indicating high genetic divergence. Nineteen serovars of Bt fell in two major clusters and remaining two formed solitary clusters in the dendogram. Clustering of Bt strains established genetic relatedness between serovars and serotypes. It has been suggested that RAPD analysis can be used for genotypic characterization of Bt to complement flagellar serotyping. 相似文献
929.
The wide-domain carbon catabolite repressor CreA indirectly controls expression of the Aspergillus nidulans xlnB gene, encoding the acidic endo-beta-(1,4)-xylanase X(24) 下载免费PDF全文
Orejas M MacCabe AP Pérez-González JA Kumar S Ramón D 《Journal of bacteriology》2001,183(5):1517-1523
The Aspergillus nidulans xlnB gene, which encodes the acidic endo-beta-(1,4)-xylanase X(24), is expressed when xylose is present as the sole carbon source and repressed in the presence of glucose. That the mutation creA(d)30 results in considerably elevated levels of xlnB mRNA indicates a role for the wide-domain repressor CreA in the repression of xlnB promoter (xlnBp) activity. Functional analyses of xlnBp::goxC reporter constructs show that none of the four CreA consensus target sites identified in xlnBp are functional in vivo. The CreA repressor is thus likely to exert carbon catabolite repression via an indirect mechanism rather than to influence xlnB expression by acting directly on xlnB. 相似文献
930.