全文获取类型
收费全文 | 15195篇 |
免费 | 1299篇 |
国内免费 | 573篇 |
专业分类
17067篇 |
出版年
2024年 | 27篇 |
2023年 | 133篇 |
2022年 | 342篇 |
2021年 | 578篇 |
2020年 | 380篇 |
2019年 | 418篇 |
2018年 | 465篇 |
2017年 | 354篇 |
2016年 | 556篇 |
2015年 | 897篇 |
2014年 | 973篇 |
2013年 | 1131篇 |
2012年 | 1310篇 |
2011年 | 1192篇 |
2010年 | 731篇 |
2009年 | 563篇 |
2008年 | 803篇 |
2007年 | 658篇 |
2006年 | 637篇 |
2005年 | 552篇 |
2004年 | 478篇 |
2003年 | 415篇 |
2002年 | 407篇 |
2001年 | 283篇 |
2000年 | 311篇 |
1999年 | 250篇 |
1998年 | 153篇 |
1997年 | 130篇 |
1996年 | 115篇 |
1995年 | 94篇 |
1994年 | 105篇 |
1993年 | 90篇 |
1992年 | 164篇 |
1991年 | 134篇 |
1990年 | 126篇 |
1989年 | 121篇 |
1988年 | 99篇 |
1987年 | 102篇 |
1986年 | 86篇 |
1985年 | 67篇 |
1984年 | 84篇 |
1983年 | 47篇 |
1982年 | 52篇 |
1981年 | 36篇 |
1980年 | 39篇 |
1979年 | 59篇 |
1978年 | 45篇 |
1977年 | 41篇 |
1975年 | 35篇 |
1973年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
102.
Besides mediating the viral entry process, the human immunodeficiency virus (HIV-1) envelope protein gp41 can bind to many host cell components and regulate cell functions. Using a yeast two-hybrid system, we screened a human bone marrow cDNA library and identified a novel gp41-binding protein, CD74 (the MHC class II-associated invariant chain). Here, we report possible biological effects mediated by interaction between gp41 and CD74. We found that HIV-1 gp41 could bind directly to host CD74 in HIV-1-infected cells, and the peptide 6358 derived from gp41 loop region (aa 597-611) could effectively block the gp41-CD74 interaction. As a result of this binding, recombinant soluble gp41 and gp41 peptide 6358 activated the CD74-mediated ERK/MAPK pathway and significantly enhanced HIV-1 infection in vitro. Conversely, the enhancing effect could be suppressed by the recombinant CD74 extracellular domain. These results reveal a novel mechanism underlying gp41 mediation of HIV-1 infection and replication. 相似文献
103.
104.
Jian-Rao Hu Mei Liu Da-Hui Wang Yan-Jun Hu Fu-Qing Tan Wan-Xi Yang 《Molecular biology reports》2013,40(12):6645-6655
The member of the kinesin-14 subfamily, KIFC1, is a carboxyl-terminal motor protein that plays an important role in the elongation of nucleus and acrosome biogenesis during the spermiogenesis of mammals. Here, we had cloned and sequenced the cDNA of a mammalian KIFC1 homologue (termed ec-KIFC1) from the total RNA of the testis of the reptile Eumeces chinensis. The full-length sequence was 2,339 bp that contained a 216 bp 5′-untranslated region (5′UTR), a 194 bp 3′-untranslated region (3′UTR) and a 1,929 bp open reading frame that encoded a special protein of 643 amino acids (aa). The calculated molecular weight of the putative ec-KIFC1 was 71 kDa and its estimated isoelectric point was 9.47. The putative ec-KIFC1 protein owns a tail domain from 1 to 116 aa, a stalk domain from 117 to 291 aa and a conserved carboxyl motor domain from 292 to 642 aa. Protein alignment demonstrated that ec-KIFC1 had 45.6, 42.8, 44.6, 36.9, 43.7, 46.4, 45.1, 55.6 and 49.8 % identity with its homologues in Mus musculus, Salmo salar, Danio rerio, Eriocheir sinensis, Rattus norvegicus, Homo sapiens, Bos taurus, Gallus gallus and Xenopus laevis, respectively. Tissue expression analysis showed the presence of ovary, heart, liver, intestine, oviduct, testis and muscle. The phylogenetic tree revealed that ec-KIFC1 was more closely related to vertebrate KIFC1 than to invertebrate KIFC1. In situ hybridization showed that the ec-KIFC1 mRNA was localized in the periphery of the nuclear membrane and the center of the nucleus in early spermatids. In mid spermatids, the ec-KIFC1 had abundant expression in the center of nucleus, and was expressed in the tail and the anterior part of spermatids. In the late spermatid, the nucleus gradually became elongated, and the ec-KIFC1 mRNA signal was still centralized in the nucleus. In mature spermatids, the signal of the ec-KIFC1 gradually became weak, and was mainly located at the tail of spermatids. Therefore, the ec-KIFC1 probably plays a critical role in the spermatogenesis of E. chinensis. 相似文献
105.
家兔腹泻生态疗法的实验观察 总被引:1,自引:0,他引:1
根据动物微生态学理论,将3株正常菌:嗜酸乳杆菌、两歧双歧杆菌、粪链球菌研制成复方生态制剂,对家免细菌性腹泻进行治疗试验。共治疗75例,治愈率为96.00%,比痢特灵对照组治愈率提高16.00%。该制剂价格低廉,无毒、副作用,使用安全可靠,是一种防治家免细菌性腹泻的较理想制剂。 相似文献
106.
107.
目的:观察鲍肤索对血管性痴呆大鼠学习与记忆能力的干预及机制。方法:制备生物鲍肤索,分剂量喂饲血管性痴呆大鼠,测试学习与记忆能力、红细胞和血红蛋白。结果:鲍肤素提高大鼠Y型迷宫测试的分值和红细胞、血红蛋白水平。结论:鲍肤素能提高血管性痴呆大鼠的学习与记忆能力和红细胞、血红蛋白水平。 相似文献
108.
Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells 总被引:2,自引:0,他引:2
Xu Y Wu F Tan L Kong L Xiong L Deng J Barbera AJ Zheng L Zhang H Huang S Min J Nicholson T Chen T Xu G Shi Y Zhang K Shi YG 《Molecular cell》2011,42(4):451-464
DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development. 相似文献
109.
Bhawana George Neeraj Jain Pei Fen Chong Jun Hou Tan Thirumaran Thanabalu 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014
Skeletal muscle formation is a multistep process involving proliferation, differentiation, alignment and fusion of myoblasts to form myotubes which fuse with additional myoblast to form myofibers. Toca-1 (Transducer of Cdc42-dependent actin assembly), is an adaptor protein which activates N-WASP in conjunction with Cdc42 to facilitate membrane invagination, endocytosis and actin cytoskeleton remodeling. Expression of Toca-1 in mouse primary myoblasts and C2C12 myoblasts was up-regulated on day 1 of differentiation and subsequently down-regulated during differentiation. Knocking down Toca-1 expression in C2C12 cells (Toca-1KD cells) resulted in a significant decrease in myotube formation and expression of shRNA-resistant Toca-1 in Toca-1KD cells rescued the myogenic defect, suggesting that the knockdown was specific and Toca-1 is essential for myotube formation. Toca-1KD cells exhibited elongated spindle-like morphology, expressed myogenic markers (MyoD and MyHC) and localized N-Cadherin at cell periphery similar to control cells suggesting that Toca-1 is not essential for morphological changes or expression of proteins critical for differentiation. Toca-1KD cells displayed prominent actin fibers suggesting a defect in actin cytoskeleton turnover necessary for cell–cell fusion. Toca-1KD cells migrated faster than control cells and had a reduced number of vinculin patches similar to N-WASPKO MEF cells. Transfection of N-WASP-expressing plasmid into Toca-1KD cells restored myotube formation of Toca-1KD cells. Thus, our results suggest that Toca-1KD cells have defects in formation of myotubes probably due to reduced activity of actin cytoskeleton regulators such as N-WASP. This is the first study to identify and characterize the role of Toca-1 in myogenesis. 相似文献
110.
通过逆转录-聚合酶链反应从我国河南省2例重叠感染HCV或HBV/HDV的献血啼中,分离到HBVNS5区的部分cDNA,对其进行序列分析比较,结果表明,河南株HGVNS5工核苷酸与两中国HGV主同源性高于国外代表株(88.5-90.6%),但由核苷酸推导的氨基酸的同源性都无明显的地区性区别。HGVNS5区氨基酸序列较保守,缺乏明显高变区,中国4株HGV在7384位发生了由C→T的变异,从而导致一个人 相似文献