全文获取类型
收费全文 | 15134篇 |
免费 | 1394篇 |
国内免费 | 2315篇 |
出版年
2024年 | 35篇 |
2023年 | 257篇 |
2022年 | 504篇 |
2021年 | 999篇 |
2020年 | 778篇 |
2019年 | 877篇 |
2018年 | 756篇 |
2017年 | 585篇 |
2016年 | 775篇 |
2015年 | 1105篇 |
2014年 | 1360篇 |
2013年 | 1364篇 |
2012年 | 1671篇 |
2011年 | 1589篇 |
2010年 | 960篇 |
2009年 | 807篇 |
2008年 | 885篇 |
2007年 | 749篇 |
2006年 | 622篇 |
2005年 | 461篇 |
2004年 | 338篇 |
2003年 | 317篇 |
2002年 | 225篇 |
2001年 | 100篇 |
2000年 | 105篇 |
1999年 | 113篇 |
1998年 | 88篇 |
1997年 | 69篇 |
1996年 | 59篇 |
1995年 | 48篇 |
1994年 | 41篇 |
1993年 | 29篇 |
1992年 | 35篇 |
1991年 | 34篇 |
1990年 | 22篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 19篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
The O-antigen gene cluster of Escherichia coli O55:H7 and identification of a new UDP-GlcNAc C4 epimerase gene 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Escherichia coli O55 is an important antigen which is often associated with enteropathogenic E. coli clones. We sequenced the genes responsible for its synthesis and identified genes for O-antigen polymerase, O-antigen flippase, four enzymes involved in GDP-colitose synthesis, and three glycosyltransferases, all by comparison with known genes. Upstream of the normal O-antigen region there is a gne gene, which encodes a UDP-GlcNAc epimerase for converting UDP-GlcNAc to UDP-GalNAc and is essential for O55 antigen synthesis. The O55 gne product has only 20 and 26% identity to the gne genes of Pseudomonas aeruginosa and E. coli O113, respectively. We also found evidence for the O55 gene cluster's having evolved from another gene cluster by gain and loss of genes. Only three of the GDP-colitose pathway genes are in the usual location, the other two being separated, although nearby. It is thought that the E. coli O157:H7 clone evolved from the O55:H7 clone in part by transfer of the O157 gene cluster into an O55 lineage. Comparison of genes flanking the O-antigen gene clusters of the O55:H7 and O157:H7 clones revealed one recombination site within the galF gene and located the other between the hisG and amn genes. Genes outside the recombination sites are 99.6 to 100% identical in the two clones, while most genes thought to have transferred with the O157 gene cluster are 95 to 98% identical. 相似文献
972.
Panin VM Shao L Lei L Moloney DJ Irvine KD Haltiwanger RS 《The Journal of biological chemistry》2002,277(33):29945-29952
O-Fucose has been identified on epidermal growth factor-like (EGF) repeats of Notch, and elongation of O-fucose has been implicated in the modulation of Notch signaling by Fringe. O-Fucose modifications are also predicted to occur on Notch ligands based on the presence of the C(2)XXGG(S/T)C(3) consensus site (where S/T is the modified amino acid) in a number of the EGF repeats of these proteins. Here we establish that both mammalian and Drosophila Notch ligands are modified with O-fucose glycans, demonstrating that the consensus site was useful for making predictions. The presence of O-fucose on Notch ligands raised the question of whether Fringe, an O-fucose specific beta 1,3-N-acetylglucosaminyltransferase, was capable of modifying O-fucose on the ligands. Indeed, O-fucose on mammalian Delta 1 and Jagged1 can be elongated with Manic Fringe in vivo, and Drosophila Delta and Serrate are substrates for Drosophila Fringe in vitro. These results raise the interesting possibility that alteration of O-fucose glycans on Notch ligands could play a role in the mechanism of Fringe action on Notch signaling. As an initial step to begin addressing the role of the O-fucose glycans on Notch ligands in Notch signaling, a number of mutations in predicted O-fucose glycosylation sites on Drosophila Serrate have been generated. Interestingly, analysis of these mutants has revealed that O-fucose modifications occur on some EGF repeats not predicted by the C(2)XXGGS/TC(3) consensus site. A revised, broad consensus site, C(2)X(3-5)S/TC(3) (where X(3-5) are any 3-5 amino acid residues), is proposed. 相似文献
973.
基于基因表达谱的肿瘤分型和特征基因选取 总被引:20,自引:0,他引:20
在分析基因表达谱数据特性的基础上,提出了一个将之用于肿瘤分子分型和选型和选取相应亚型特征基因的策略。该策略包括三个步骤:首先采用一个无监督的基因过滤算法以降低用于分型计算的数据的噪声,其次提出了一个概率模型对样本中的分类结构进行建模,最后基于聚类的结果采用相对熵的方法获得对分类贡献大的基因作为特征基因,应用该策略对两个公开发表的数据集进行了再挖掘,结果表明不但获得了其他方法可以得到的信息,而且还提供了更精细、更具有显著生物学意义的信息,具有明显的优越性。 相似文献
974.
The inhibition of lung cancer cell growth by intracellular immunization with LC—1 ScFv 总被引:2,自引:0,他引:2
INTRODUCTIONLung cancer remains the leading cause of can-cer mortaIity in the world, accounting for more thanone sixth of cancer deaths in the world[1]. Antibod-ies have been proved to be a powerful tool fOr thestudy of 1ung cancer. A monoclonal IgM antibody,LC-1, was obtained in our laboratory. It can reactat a high rate with all four pathological types of lungcancers, including lung adenocarcinoma, 1ung squamous carcinoma, large cell lung cancer and smaIlcell lung cancert but not wit… 相似文献
975.
976.
Stu1p is physically associated with beta-tubulin and is required for structural integrity of the mitotic spindle
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Formation of the bipolar mitotic spindle relies on a balance of forces acting on the spindle poles. The primary outward force is generated by the kinesin-related proteins of the BimC family that cross-link antiparallel interpolar microtubules and slide them past each other. Here, we provide evidence that Stu1p is also required for the production of this outward force in the yeast Saccharomyces cerevisiae. In the temperature-sensitive stu1-5 mutant, spindle pole separation is inhibited, and preanaphase spindles collapse, with their previously separated poles being drawn together. The temperature sensitivity of stu1-5 can be suppressed by doubling the dosage of Cin8p, a yeast BimC kinesin-related protein. Stu1p was observed to be a component of the mitotic spindle localizing to the midregion of anaphase spindles. It also binds to microtubules in vitro, and we have examined the nature of this interaction. We show that Stu1p interacts specifically with beta-tubulin and identify the domains required for this interaction on both Stu1p and beta-tubulin. Taken together, these findings suggest that Stu1p binds to interpolar microtubules of the mitotic spindle and plays an essential role in their ability to provide an outward force on the spindle poles. 相似文献
977.
The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase 总被引:26,自引:0,他引:26
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lei K Nimnual A Zong WX Kennedy NJ Flavell RA Thompson CB Bar-Sagi D Davis RJ 《Molecular and cellular biology》2002,22(13):4929-4942
Targeted gene disruption studies have established that the c-Jun NH(2)-terminal kinase (JNK) signaling pathway is required for stress-induced release of mitochondrial cytochrome c and apoptosis. Here we demonstrate that activated JNK is sufficient to induce rapid cytochrome c release and apoptosis. However, activated JNK fails to cause death in cells deficient of members of the Bax subfamily of proapoptotic Bcl2-related proteins. Furthermore, exposure to stress fails to activate Bax, cause cytochrome c release, and induce death in JNK-deficient cells. These data demonstrate that proapoptotic members of the Bax protein subfamily are essential for JNK-dependent apoptosis. 相似文献
978.
Interferon- (IFN),4 a cytokine with modulatory activities on many cell types, is useful for treating many types of cancer and infectious diseases. This study investigates whether modification of a protein, using IFN as an example, with a lipophilic group can alter its distribution and kinetic properties in the body. Ser163 of IFN2a was mutated to Cys to generate a free sulfhydryl group for site-specific chemical modification. IFN2a(S163C) was conjugated by iodoacetamide derivatives of varying lengths, and the modified IFN2a was purified by gel filtration chromatography. The biological activities of IFN2a(S163C) and lipophilized IFN2a(S163C) were similar to that of IFN2a, as evidenced by their inhibitory effects on the growth of Daudi cells and on the replication of vesicular stomatitis virus in Madin-Darby bovine kidney cells. Lipophilized IFN2a(S163C) bound to human serum albumin and cell membranes more readily than did IFN2a. Future experiments will investigate whether lipophilized IFN2a(S163C) has improved pharmacokinetic properties. 相似文献
979.
Zhao L Cuff CA Moss E Wille U Cyrus T Klein EA Praticò D Rader DJ Hunter CA Puré E Funk CD 《The Journal of biological chemistry》2002,277(38):35350-35356
Targeted gene disruption or overexpression of 12/15-lipoxygenase in mice on the genetic background of apolipoprotein E or low density lipoprotein-receptor (LDL-R) deficiency has implicated 12/15-lipoxygenase in atherogenesis. The data support indirectly a role for 12/15-lipoxygenase in the oxidative modification of low density lipoprotein. In this study we set out to explore other potential mechanisms for 12/15-lipoxygenase in atherosclerosis using apolipoprotein B mRNA editing catalytic polypeptide-1/LDL-R double-deficient mice, a model highly related to the human condition of familial hypercholesterolemia. 12/15-Lipoxygenase deficiency in this strain led to approximately 50% decrease in aortic lesions in male and female mice at 8 months on a chow diet in the absence of cholesterol differences. While studying 12/15-lipoxygenase-deficient macrophages in culture, we discovered a remarkable selective defect (75-90% decrease) in interleukin-12 production but not in tumor necrosis factor-alpha or nitric oxide release, in response to lipopolysaccharide in the presence or absence of interferon-gamma priming. The lipopolysaccharide/interferon-gamma response was associated with a 33-50% decrease in nuclear interferon consensus sequence-binding protein, which is consistent with interferon consensus sequence-binding protein containing protein complex-dependent regulation of the interleukin-12 p40 gene. The decrease in interleukin-12 production was recapitulated in vivo in mouse aortas of the triple knockout group and was reflected in a marked decrease in interferon-gamma expression. The data provide support for a novel mechanism linking the 12/15-lipoxygenase pathway to a known immunomodulatory Th1 cytokine in atherogenesis. 相似文献
980.