全文获取类型
收费全文 | 636篇 |
免费 | 41篇 |
专业分类
677篇 |
出版年
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 3篇 |
2016年 | 19篇 |
2015年 | 14篇 |
2014年 | 19篇 |
2013年 | 41篇 |
2012年 | 27篇 |
2011年 | 32篇 |
2010年 | 27篇 |
2009年 | 15篇 |
2008年 | 31篇 |
2007年 | 22篇 |
2006年 | 26篇 |
2005年 | 21篇 |
2004年 | 19篇 |
2003年 | 27篇 |
2002年 | 19篇 |
2001年 | 21篇 |
2000年 | 12篇 |
1999年 | 15篇 |
1998年 | 8篇 |
1997年 | 11篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 19篇 |
1990年 | 12篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 10篇 |
1984年 | 12篇 |
1983年 | 3篇 |
1981年 | 8篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1967年 | 2篇 |
1962年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有677条查询结果,搜索用时 15 毫秒
1.
The apparent conductance (Kss, in W.m-2.degrees C-1) of a given region of superficial shell (on the thigh, fat + skin) was determined on four nonsweating and nonshivering subjects, resting and exercising (200 W) in water [water temperature (Tw) 22-23 degrees C] Kss = Hss/(Tsf-Tsk) where Hss is the skin-to-water heat flow directly measured by heat flow transducers and Tsf and Tsk are the temperatures of the subcutaneous fat at a known depth below the skin surface and of the skin surface, respectively. The convective heat flow (qc) through the superficial shell was then estimated as qc = (Tsf - Tsk).(Kss - Kss,min), assuming that at rest Kss was minimal (Kss,min) and resting qc = 0. The duration of immersion was set to allow rectal temperature (Tre) to reach approximately 37 degrees C at the end of rest and approximately 38 degrees C at the end of exercise. Except at the highest Tw used, Kss at the start of exercise was always Kss,min and averaged 51 W.m-2.degrees C-1 (range 33-57 W.m-2.degrees C-1) across subjects, and qc was zero. At the end of exercise at the highest Tw used for each subject, Kss averaged 97 W.m-2.degrees C-1 (range 77-108 W.m-2.degrees C-1) and qc averaged 53% (range 48-61%) of Hss (mean Hss = 233 W.m-2).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
2.
3.
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
4.
Summary Previous work has shown that the monoclonal antibody 22/18 identifies progenitor cells (blastemal cells) which depend on the nerve for their division in the early stages of limb regeneration in the newt,Notophthalmus viridescens. This antibody also reacts with cultured cells derived from the newt limb, and the intensity of immunoreactivity appears related to cell density and differentiation into myotubes. We report here that the monoclonal antibody 22/18 recognizes a polypeptide (22/18 antigen) which is intracellular and filamentous. Double staining of cells with 22/18 monoclonal antibody and antibodies against various cytoskeletal components indicates that the epitope is expressed on an intermediate filament component. Although this antibody is specific for blastemal cells in cryostat sections of the regenerating limb, its reactivity on immunoblots is not confined to this tissue. The 22/18 antigen is differentially affected by aldehyde fixatives distinguished by the spacing of their reactive groups. While formaldehyde fixation impairs detection of the antigen, ethylene glycol-bis[succinic acid n-hydroxysuccinimide ester] reveals the antigen in sections of normal and regenerating limbs in a distribution that is consistent with the one obtained from immunoblots. We suggest that the 22/18 monoclonal antibody detects a change in protein conformation, probably related to changes in the physiological state of the cell, that occurs transiently during regeneration and possibly during development. 相似文献
5.
Transient expression of simple epithelial keratins by mesenchymal cells of regenerating newt limb 总被引:7,自引:0,他引:7
Structural proteins of the intermediate filament family are an early indicator of differentiation before organogenesis becomes apparent. Keratin intermediate filaments are characteristically expressed only by epithelial and not by mesenchymal cells. Here we show, using monoclonal antibodies, a transient expression of the keratin pair 8 and 18 in a population of mesenchymal cells in the regenerating newt limb, specifically in the undifferentiated progenitor cells (blastemal cells) which give rise to the new tissues. These keratins are also expressed in cultured limb cells that can differentiate into muscle. In contrast no reactivity with anti-keratin 8 and 18 antibodies was observed in the newt limb bud at an early stage of development, indicating a molecular difference between the developing and regenerating limb. The molecular weights of the newt proteins detected by these antibodies are very similar to those of human keratins 8 and 18, further supporting the immunocytochemical evidence that the newt homologs of these keratins are expressed in blastemal cells. This is the first demonstration of keratin expression in mesenchymal progenitor cells in an adult animal. 相似文献
6.
U. Brand L. Brandes V. Koch T. Kullik B. Reinhardt F. Rüther T. Scheper K. Schügerl S. Wang X. Wu R. Ferretti S. Prasad D. Wilhelm 《Applied microbiology and biotechnology》1991,36(2):167-172
Summary Single and multisensor field effect transistors (FET) with a pH-sensitive Si/SiO2/Si3N4/Ta2O5-gate and reference electrode (for single sensor) were developed and used for manufacturing the following biological (Bio)-FETs: for glucose analysis, glucose oxidase-FET (GOD-FET); for urea analysis, urease-FET; and for cephalosporin C analysis, cephalosporinase-FET. The GOD-FETs were integrated into flow injection analysis (FIA) of the Eppendorf variables analyser (EVA) system and used for monitoring the glucose concentration in microbial cultivation and production processes with recombinant Escherichia coli K12 MF, recombinant E. coli JM103, Saccharomyces cerevisiae H620, and Candida boidinii. Urease-FET-FIA was used to monitor the urea concentration in a simulated cultivation of Cephalosporium acremonium and urease-FET-FIA and GOD-FET-FIA for the monitoring of urea and glucose concentrations in simulated S. cerevisiae cultivations. 相似文献
7.
Electrotransformation was used to introduce both plasmid and linear DNA into Streptococcus pyogenes. The method was optimized using strain NZ131, for which transformation frequencies up to 10(7) per micrograms of plasmid DNA were obtained. A linear fragment of DNA, containing the streptokinase gene (ska) in which an internal fragment had been replaced with an erythromycin resistance gene (erm), was transformed into strain NZ131 with a frequency of 10(3) per micrograms DNA. The introduction of linear DNA into S. pyogenes by electrotransformation should be useful for future genetic analyses as well as targeted gene replacement. 相似文献
8.
Muscle adenylate kinase catalyzes adenosine 5'-tetraphosphate synthesis from ATP and ADP 总被引:1,自引:0,他引:1
Muscle adenylate kinases from rabbit and porcine sources were found by NMR to catalyze the formation of adenosine tetraphosphate (5'AdoP4) from adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The reaction was completely reversible, with an equilibrium constant of approx. 0.1 at 30 degrees C. The synthesis of 5'AdoP4 from ATP and ADP occurred very slowly, taking over 12 h to reach equilibrium under the conditions used in this study. The sources of micromolar concentrations of 5'AdoP4 found in biological tissues is unknown: potentially, the slow adenylate-kinase-catalyzed breakdown and synthesis of 5'AdoP4 may serve as an important regulator of the steady-state concentration of 5'AdoP4 in muscle tissue. 相似文献
9.
The electrophoretic separation of protein variants having slightly different mobilities is a basic tool of biochemical population genetics. In certain situations it is difficult to determine how to classify the variants as alleles of a number of genetic loci, that is, as variant subsets within each of which the Mendelian laws hold. In this article, we develop and analyze a series of algorithms for solving various versions and generalizations of this problem of optimal classification. 相似文献
10.
Physiological profile of world-class high-altitude climbers 总被引:1,自引:0,他引:1
O Oelz H Howald P E Di Prampero H Hoppeler H Claassen R Jenni A Bühlmann G Ferretti J C Brückner A Veicsteinas 《Journal of applied physiology》1986,60(5):1734-1742
The functional characteristics of six world-class high-altitude mountaineers were assessed 2-12 mo after the last high-altitude climb. Each climber on one or several occasions had reached altitudes of 8,500 m or above without supplementary O2. Static and dynamic lung volumes and right and left echocardiographic measurements were found to be within normal limits of sedentary controls (SC). Muscle fiber distribution was 70% type I, 22% type IIa, and 7% type IIb. Mean muscle fiber cross-sectional area was significantly smaller than that of SC (-15%) and of long-distance runners (LDR, -51%). The number of capillaries per unit cross-sectional area was significantly greater than that of SC (+ 40%). Total mitochondrial volume was not significantly different from that of SC, but its subsarcolemmal component was equal to that of LDR. Average maximal O2 consumption was 60 +/- 6 ml X kg-1 X min-1, which is between the values of SC and LDR. Average maximal anaerobic power was 28 +/- 2.5 W X kg-1, which is equal to that of SC and 40% lower that that of competitive high jumpers. All subjects were characterized by resting hyperventilation both in normoxia and in moderate (inspired O2 partial pressure = 77 Torr) hypoxia resulting in higher oxyhemoglobin saturation levels in hypoxia. The ventilatory response to four tidal volumes of pure O2 was similar to that of SC. It is concluded that elite high-altitude climbers do not have physiological adaptations to high altitude that justify their unique performance. 相似文献