全文获取类型
收费全文 | 2263篇 |
免费 | 232篇 |
国内免费 | 2篇 |
专业分类
2497篇 |
出版年
2023年 | 17篇 |
2022年 | 35篇 |
2021年 | 53篇 |
2020年 | 24篇 |
2019年 | 33篇 |
2018年 | 44篇 |
2017年 | 40篇 |
2016年 | 53篇 |
2015年 | 79篇 |
2014年 | 93篇 |
2013年 | 141篇 |
2012年 | 135篇 |
2011年 | 126篇 |
2010年 | 74篇 |
2009年 | 80篇 |
2008年 | 95篇 |
2007年 | 82篇 |
2006年 | 71篇 |
2005年 | 99篇 |
2004年 | 87篇 |
2003年 | 75篇 |
2002年 | 75篇 |
2001年 | 41篇 |
2000年 | 46篇 |
1999年 | 44篇 |
1998年 | 38篇 |
1997年 | 35篇 |
1996年 | 24篇 |
1995年 | 28篇 |
1994年 | 27篇 |
1993年 | 25篇 |
1992年 | 32篇 |
1991年 | 36篇 |
1990年 | 38篇 |
1989年 | 25篇 |
1988年 | 24篇 |
1987年 | 32篇 |
1986年 | 22篇 |
1985年 | 18篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 17篇 |
1979年 | 19篇 |
1978年 | 20篇 |
1977年 | 17篇 |
1973年 | 15篇 |
1971年 | 16篇 |
1969年 | 14篇 |
1968年 | 15篇 |
1967年 | 16篇 |
排序方式: 共有2497条查询结果,搜索用时 0 毫秒
1.
2.
3.
4.
Davide Danovi Amos Folarin Sabine Gogolok Christine Ender Ahmed M. O. Elbatsh P?r G. Engstr?m Stefan H. Stricker Sladjana Gagrica Ana Georgian Ding Yu Kin Pong U Kevin J. Harvey Patrizia Ferretti Patrick J. Paddison Jane E. Preston N. Joan Abbott Paul Bertone Austin Smith Steven M. Pollard 《PloS one》2013,8(10)
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. 相似文献
5.
6.
7.
Indirect evidence suggests that legumes can adjust rapidly theresistance of their root nodules to O2 diffusion. Here we describeexperiments using O2 specific micro-electrodes and dark fieldmicroscopy to study directly the operation of this diffusionbarrier. The O2 concentration sensed by the electrode decreasedsharply in the region of the inner cortex and was less than1.0 mmol m3 throughout the infected tissue in nodulesof both pea (Pisum sativum) and french bean (Phaseolus vulgaris).In a number of experiments the ambient O2 concentration wasincreased to 40% while the electrode tip was just inside theinner cortex. In 13 out of 21 cases the O2 concentration atthis position either remained low and unchanged or increasedirreversibly to near ambient values. In the remaining casesthe O2 concentration increased after 1 to 2.5 min and then decreasedto its former value. These results are ascribed to an increasein resistance of the barrier in response to increased O2 fluxinto the nodule. It was shown microscopically that air spacesboth at the boundary between the infected zone and the innercortex, and within the infected zone started to disappear 3min after nodules were exposed to high ambient O2 concentrationsand had disappeared completely after 8 min. These spaces werenot changed by exposure of the nodule for 10 min to either N2or air. Key words: Oxygen, root nodules, air spaces 相似文献
8.
Evolution of the 28S ribosomal RNA gene in anurans: regions of variability and their phylogenetic implications 总被引:1,自引:0,他引:1
Fifteen restriction sites were mapped to the 28S ribosomal RNA gene of
individuals representing 54 species of frogs, two species of salamanders, a
caecilian, and a lungfish. Eight of these sites were present in all species
examined, and two were found in all but one species. Alignment of these
conserved restriction sites revealed, among anuran 28S rRNA genes, five
regions of major length variation that correspond to four of 12 previously
identified divergent domains of this gene. One of the divergent domains
(DD8) consists of two regions of length variation separated by a short
segment that is conserved at least throughout tetrapods. Most of the
insertions, deletions, and restriction-site variations identified in the
28S gene will require sequence-level analysis for a detailed reconstruction
of their history. However, an insertion in DD9 that is coextensive with
frogs in the suborder Neobatrachia, a BstEII site that is limited to
representatives of two leptodactylid subfamilies, and a deletion in DD10
that is found only in three ranoid genera are probably synapomorphies.
相似文献
9.
10.
Epidermal growth factor (EGF) stimulates EGF receptor synthesis 总被引:13,自引:0,他引:13
H S Earp K S Austin J Blaisdell R A Rubin K G Nelson L W Lee J W Grisham 《The Journal of biological chemistry》1986,261(11):4777-4780
Epidermal growth factor (EGF) binds to the extracellular domain of a specific 170,000-dalton transmembrane glycoprotein; this results in rapid removal of both ligand and receptor from the cell surface. In WB cells, a rat hepatic epithelial cell line, ligand-directed receptor internalization leads to receptor degradation. We tested whether the EGF receptor was replenished at a constitutive or enhanced rate following EGF binding by immunoprecipitating biosynthetically labeled EGF receptor from cells cultured with [35S]methionine. EGF stimulated receptor synthesis within 2 h in a dose-dependent manner; this was particularly evident when examining the nascent form of the receptor. To determine the site of EGF action, total WB cell RNA was transferred to nitrocellulose paper after electrophoresis and was hybridized to cDNA probes from both the external and cytoplasmic coding regions of the human EGF receptor. EGF increased receptor mRNA by 3-5-fold. Therefore, at least in some cells, the surface action of EGF that leads to EGF receptor degradation is counterbalanced by a positive effect on receptor synthesis. 相似文献