全文获取类型
收费全文 | 5185篇 |
免费 | 623篇 |
国内免费 | 1篇 |
出版年
2021年 | 51篇 |
2018年 | 62篇 |
2017年 | 51篇 |
2016年 | 92篇 |
2015年 | 156篇 |
2014年 | 157篇 |
2013年 | 202篇 |
2012年 | 223篇 |
2011年 | 237篇 |
2010年 | 149篇 |
2009年 | 129篇 |
2008年 | 185篇 |
2007年 | 163篇 |
2006年 | 183篇 |
2005年 | 155篇 |
2004年 | 151篇 |
2003年 | 124篇 |
2002年 | 184篇 |
2001年 | 170篇 |
2000年 | 159篇 |
1999年 | 148篇 |
1998年 | 68篇 |
1997年 | 45篇 |
1996年 | 62篇 |
1995年 | 82篇 |
1994年 | 59篇 |
1993年 | 72篇 |
1992年 | 134篇 |
1991年 | 117篇 |
1990年 | 137篇 |
1989年 | 98篇 |
1988年 | 119篇 |
1987年 | 109篇 |
1986年 | 91篇 |
1985年 | 100篇 |
1984年 | 81篇 |
1983年 | 74篇 |
1982年 | 76篇 |
1981年 | 73篇 |
1980年 | 67篇 |
1979年 | 95篇 |
1978年 | 91篇 |
1977年 | 67篇 |
1976年 | 64篇 |
1975年 | 56篇 |
1973年 | 49篇 |
1972年 | 58篇 |
1971年 | 50篇 |
1968年 | 40篇 |
1967年 | 43篇 |
排序方式: 共有5809条查询结果,搜索用时 687 毫秒
881.
I. Klein J. Welink W. J. F. van der Vijgh 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1993,622(2):249-253
The cytostatic agent Elsamitrucin is a new fermentation product active in a variety of in vivo tumor models of murine and human origin. To determine its pharmacokinetics during the clinical phase I trial, an HPLC procedure was developed and validated. Plasma samples were extracted after addition of the internal standard, i.e. the analog Chartreusin. Urine samples were injected without extraction of the samples. Because of the wide concentration range of Elsamitrucin in the plasma samples two standard curves were used: up to 100 nM and from 100–1000 nM. Recoveries of Elsamitrucin from plasma were 87% and 74% for concentrations lower and higher than 100 nM, respectively. The detection limits were 1 nM in plasma and 7.5 nM in urine at a signal-to-noise ratio of 3. The accuracy ranged from 95–107% for plasma and from 96–104% for urine. The within-day precision was 4.8% and 2.8% in plasma and urine, respectively. The between-day precision was 4.4% and 7.1% in plasma and urine, respectively. The method proved to be sufficiently sensitive, specific and accurate for analysis of clinical samples for pharmacokinetic purposes. 相似文献
882.
Aysun Çapcı Karagöz Christoph Reiter Ean-Jeong Seo Lisa Gruber Friedrich Hahn Maria Leidenberger Volker Klein Frank Hampel Oliver Friedrich Manfred Marschall Barbara Kappes Thomas Efferth Svetlana B. Tsogoeva 《Bioorganic & medicinal chemistry》2018,26(12):3610-3618
Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high potency of these hybrids and encourages further use of the hybridization concept in applied pharmacological research. 相似文献
883.
884.
F. S. van den Brink A. D. Magan P. G. Noordzij C. Zivelonghi P. Agostoni F. D. Eefting J. M. ten Berg M. J. Suttorp B. R. Rensing J. P. van Kuijk P. Klein E. Scholten J. A. S. van der Heyden 《Netherlands heart journal》2018,26(2):76-84
Introduction
Primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) can cause great haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide haemodynamic support in patients with STEMI but data on outcome and complications are scarce.Methods
An in-hospital registry was conducted enrolling all patients receiving VA-ECMO. Patients were analysed for medical history, mortality, neurological outcome, complications and coronary artery disease.Results
Between 2011 and 2016, 12 patients underwent pPCI for STEMI and received VA-ECMO for haemodynamic support. The majority of the patients were male (10/12) with a median age of 63 (47–75) years and 4 of the 12 patients had a history of coronary artery disease. A cardiac arrest was witnessed in 11 patients. The left coronary artery was compromised in 8 patients and 4 had right coronary artery disease. All patients were in Killip class IV. Survival to discharge was 67% (8/12), 1?year survival was 42% (5/12), 2 patients have not yet reached the 1?year survival point but are still alive and 1 patient died within a year after discharge. All-cause mortality was 42% (5/12) of which mortality on ECMO was 33% (4/12). Patient-related complications occurred in 6 of the 12 patients: 1 patient suffered major neurological impairment, 2 patients suffered haemorrhage at the cannula site, 2 patients had limb ischaemia and 1 patient had a haemorrhage elsewhere. There were no VA-ECMO hardware malfunctions.Conclusion
VA-ECMO in pPCI for STEMI has a high survival rate and neurological outcome is good, even when the patient is admitted with a cardiac arrest.885.
886.
887.
Danusa Mar Arcego Ana Paula Toniazzo Rachel Krolow Carine Lampert Carolina Berlitz Emily dos Santos Garcia Fabrício do Couto Nicola Juliana Bender Hoppe Mariana Maier Gaelzer Caroline Peres Klein Camilla Lazzaretti Carla Dalmaz 《Molecular neurobiology》2018,55(4):2740-2753
During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in βIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly. 相似文献
888.
Zonghua Luo Xuyi Yue Hao Yang Hui Liu Robyn S. Klein Zhude Tu 《Bioorganic & medicinal chemistry letters》2018,28(3):488-496
Eleven new sphingosine 1-phosphate receptor 2 (S1PR2) ligands were synthesized by modifying lead compound N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) and their binding affinities toward S1PRs were determined in vitro using [32P]S1P and cell membranes expressing recombinant human S1PRs. Among these ligands, 35a (IC50?=?29.1?±?2.6?nM) and 35b (IC50?=?56.5?±?4.0?nM) exhibit binding potency toward S1PR2 comparable to JTE-013 (IC50?=?58.4?±?7.4?nM) with good selectivity for S1PR2 over the other S1PRs (IC50?>?1000?nM). Further optimization of these analogues may identify additional and more potent and selective compounds targeting S1PR2. 相似文献
889.
890.
Colin Klein 《Biology & philosophy》2018,33(5-6):36
Distinguishing mechanistic components from mere causally relevant background conditions remains a difficulty for mechanistic accounts of explanation. By distinguishing resources from mechanical parts, I argue that we can more effectively draw this boundary. Further, the distinction makes obvious that there are distinctive resource explanations which are not captured by a traditional part-based mechanistic account. While this suggests a straightforward extension of the mechanistic model, I argue that incorporating resources and resource explanations requires moving beyond the purely local account of levels that some mechanists advocate. 相似文献