全文获取类型
收费全文 | 3497篇 |
免费 | 338篇 |
国内免费 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 11篇 |
2022年 | 50篇 |
2021年 | 80篇 |
2020年 | 52篇 |
2019年 | 45篇 |
2018年 | 81篇 |
2017年 | 78篇 |
2016年 | 124篇 |
2015年 | 226篇 |
2014年 | 224篇 |
2013年 | 255篇 |
2012年 | 317篇 |
2011年 | 339篇 |
2010年 | 215篇 |
2009年 | 177篇 |
2008年 | 249篇 |
2007年 | 256篇 |
2006年 | 233篇 |
2005年 | 161篇 |
2004年 | 154篇 |
2003年 | 157篇 |
2002年 | 137篇 |
2001年 | 20篇 |
2000年 | 12篇 |
1999年 | 28篇 |
1998年 | 25篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有3836条查询结果,搜索用时 812 毫秒
131.
This study assessed the effectiveness of operant conditioning in training three species of captive callitrichid primates (Leontopithecus rosalia, Callithrix geoffroyi, and Saguinus imperator) to urinate on demand. There were three goals to the study: 1) to develop a system for quantitatively assessing positive reinforcement training; 2) to ascertain whether or not positive reinforcement techniques can be used to train callitrichid monkeys to urinate on demand, and if so, how many training sessions are required; and 3) to determine the effect on urination behavior of the trainer entering the cage to collect a urine sample. Positive reinforcement with a continuous reinforcement schedule was used to capture a natural behavior: urination. Training sessions (30 min each) were conducted at dawn thrice weekly during five consecutive phases: habituation, control, training (animals were rewarded for urinating), maintenance (animals had reached a defined training criteria and continued to be rewarded for urinating), and collection (animals were rewarded for urinating, and the trainer entered the cage to collect the sample). The numbers of 30-min training sessions required to train the three monkey species (L. rosalia, C. geoffroyi, and S. imperator) were five, six, and eight, respectively. For the three species, the mean number of urinations per animal was significantly greater during the training, maintenance, and collection phases compared to the control phase. However, the three species differed significantly in the manner in which the rates of urination changed across the five phases. A higher proportion of subjects urinated during the training, maintenance, and collection phases compared to the control phase. Latency to first urination varied significantly across the five phases, with significantly reduced latencies to urinate during the training, maintenance, and collection phases compared to the control phase. The entry of the trainer into the cage to collect the urine sample did not appear to alter urination behavior. We demonstrate that operant conditioning techniques, which typically incur minimal cost, time investment, and disturbance, can be used to increase the quantity of urine samples collected for physiological analysis, the proportion of animals that urinate, and the speed of sample collection. 相似文献
132.
Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development 总被引:10,自引:0,他引:10
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)
Gangloff YG Mueller M Dann SG Svoboda P Sticker M Spetz JF Um SH Brown EJ Cereghini S Thomas G Kozma SC 《Molecular and cellular biology》2004,24(21):9508-9516
The mammalian target of rapamycin (mTOR) is a key component of a signaling pathway which integrates inputs from nutrients and growth factors to regulate cell growth. Recent studies demonstrated that mice harboring an ethylnitrosourea-induced mutation in the gene encoding mTOR die at embryonic day 12.5 (E12.5). However, others have shown that the treatment of E4.5 blastocysts with rapamycin blocks trophoblast outgrowth, suggesting that the absence of mTOR should lead to embryonic lethality at an earlier stage. To resolve this discrepancy, we set out to disrupt the mTOR gene and analyze the outcome in both heterozygous and homozygous settings. Heterozygous mTOR (mTOR(+/-)) mice do not display any overt phenotype, although mouse embryonic fibroblasts derived from these mice show a 50% reduction in mTOR protein levels and phosphorylation of S6 kinase 1 T389, a site whose phosphorylation is directly mediated by mTOR. However, S6 phosphorylation, raptor levels, cell size, and cell cycle transit times are not diminished in these cells. In contrast to the situation in mTOR(+/-) mice, embryonic development of homozygous mTOR(-/-) mice appears to be arrested at E5.5; such embryos are severely runted and display an aberrant developmental phenotype. The ability of these embryos to implant corresponds to a limited level of trophoblast outgrowth in vitro, reflecting a maternal mRNA contribution, which has been shown to persist during preimplantation development. Moreover, mTOR(-/-) embryos display a lesion in inner cell mass proliferation, consistent with the inability to establish embryonic stem cells from mTOR(-/-) embryos. 相似文献
133.
Rap2B-dependent stimulation of phospholipase C-epsilon by epidermal growth factor receptor mediated by c-Src phosphorylation of RasGRP3 总被引:1,自引:0,他引:1
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)
Stope MB Vom Dorp F Szatkowski D Böhm A Keiper M Nolte J Oude Weernink PA Rosskopf D Evellin S Jakobs KH Schmidt M 《Molecular and cellular biology》2004,24(11):4664-4676
Receptor tyrosine kinase regulation of phospholipase C-epsilon (PLC-epsilon), which is under the control of Ras-like and Rho GTPases, was studied with HEK-293 cells endogenously expressing PLC-coupled epidermal growth factor (EGF) receptors. PLC and Ca(2+) signaling by the EGF receptor, which activated both PLC-gamma1 and PLC-epsilon, was specifically suppressed by inactivation of Ras-related GTPases with clostridial toxins and expression of dominant-negative Rap2B. EGF induced rapid and sustained GTP loading of Rap2B, binding of Rap2B to PLC-epsilon, and Rap2B-dependent translocation of PLC-epsilon to the plasma membrane. GTP loading of Rap2B by EGF was inhibited by chelation of intracellular Ca(2+) and expression of lipase-inactive PLC-gamma1 but not of PLC-epsilon. Expression of RasGRP3, a Ca(2+)/diacylglycerol-regulated guanine nucleotide exchange factor for Ras-like GTPases, but not expression of various other exchange factors enhanced GTP loading of Rap2B and PLC/Ca(2+) signaling by the EGF receptor. EGF induced tyrosine phosphorylation of RasGRP3, but not RasGRP1, apparently caused by c-Src; inhibition of c-Src interfered with EGF-induced Rap2B activation and PLC stimulation. Collectively, these data suggest that the EGF receptor triggers activation of Rap2B via PLC-gamma1 activation and tyrosine phosphorylation of RasGRP3 by c-Src, finally resulting in stimulation of PLC-epsilon. 相似文献
134.
135.
Srinivas S Rodriguez T Clements M Smith JC Beddington RS 《Development (Cambridge, England)》2004,131(5):1157-1164
The anterior visceral endoderm (AVE) of the mouse embryo is a specialised extra-embryonic tissue that is essential for anterior patterning of the embryo. It is characterised by the expression of anterior markers such as Hex, Cerberus-like and Lhx1. At pre-gastrula stages, cells of the AVE are initially located at the distal tip of the embryo, but they then move unilaterally to the future anterior. This movement is essential for converting the existing proximodistal axis into an anteroposterior axis. To investigate this process, we developed a culture system capable of imaging embryos in real time with single cell resolution. Our results show that AVE cells continuously change shape and project filopodial processes in their direction of motion, suggesting that they are actively migrating. Their proximal movement stops abruptly at the junction of the epiblast and extra-embryonic ectoderm, whereupon they move laterally. Confocal microscope images show that AVE cells migrate as a single layer in direct contact with the epiblast, suggesting that this tissue might provide directional cues. Together, these results show that the anteroposterior axis is correctly positioned by the active movement of cells of the AVE in response to cues from their environment, and by a 'barrier' to their movement that provides an endpoint for this migration. 相似文献
136.
137.
Rohrlack T Christoffersen K Kaebernick M Neilan BA 《Applied and environmental microbiology》2004,70(8):5047-5050
Laboratory experiments identified microviridin J as the source of a fatal molting disruption in Daphnia species organisms feeding on Microcystis cells. The molting disruption was presumably linked to the inhibitory effect of microviridin J on daphnid proteases, suggesting that hundreds of further cyanobacterial protease inhibitors must be considered potentially toxic to zooplankton. 相似文献
138.
139.
Nazaré M Essrich M Will DW Matter H Ritter K Urmann M Bauer A Schreuder H Dudda A Czech J Lorenz M Laux V Wehner V 《Bioorganic & medicinal chemistry letters》2004,14(16):4191-4195
A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is described. Structural requirements for neutral ligands, which bind in the S1 pocket of factor Xa were investigated with the 2-carboxyindole scaffold. This privileged fragment assembly approach yielded a set of equipotent, selective inhibitors with structurally diverse neutral P1 substituents. 相似文献
140.
Vanden Eynde JJ Mayence A Huang TL Collins MS Rebholz S Walzer PD Cushion MT 《Bioorganic & medicinal chemistry letters》2004,14(17):4545-4548
A series of pentamidine congeners has been synthesized and screened for their in vitro activity against Pneumocystis carinii. Among the tested compounds, bisbenzamidines linked by a flexible pentanediamide or hexanediamide chain (7 and 9) emerged as exceptionally potent agents that were more effective and less toxic than pentamidine in the assays described in this study. 相似文献