全文获取类型
收费全文 | 3276篇 |
免费 | 226篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 97篇 |
妇产科学 | 48篇 |
基础医学 | 557篇 |
口腔科学 | 40篇 |
临床医学 | 481篇 |
内科学 | 605篇 |
皮肤病学 | 39篇 |
神经病学 | 414篇 |
特种医学 | 90篇 |
外科学 | 362篇 |
综合类 | 14篇 |
预防医学 | 284篇 |
眼科学 | 53篇 |
药学 | 223篇 |
中国医学 | 2篇 |
肿瘤学 | 187篇 |
出版年
2024年 | 7篇 |
2023年 | 31篇 |
2022年 | 35篇 |
2021年 | 89篇 |
2020年 | 69篇 |
2019年 | 89篇 |
2018年 | 91篇 |
2017年 | 61篇 |
2016年 | 88篇 |
2015年 | 88篇 |
2014年 | 107篇 |
2013年 | 180篇 |
2012年 | 239篇 |
2011年 | 266篇 |
2010年 | 124篇 |
2009年 | 130篇 |
2008年 | 190篇 |
2007年 | 211篇 |
2006年 | 186篇 |
2005年 | 169篇 |
2004年 | 174篇 |
2003年 | 171篇 |
2002年 | 171篇 |
2001年 | 31篇 |
2000年 | 43篇 |
1999年 | 30篇 |
1998年 | 37篇 |
1997年 | 25篇 |
1996年 | 21篇 |
1995年 | 25篇 |
1994年 | 17篇 |
1993年 | 9篇 |
1992年 | 21篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 18篇 |
1983年 | 10篇 |
1982年 | 15篇 |
1981年 | 8篇 |
1978年 | 14篇 |
1975年 | 15篇 |
1974年 | 8篇 |
1970年 | 7篇 |
1937年 | 7篇 |
1931年 | 7篇 |
1928年 | 7篇 |
排序方式: 共有3519条查询结果,搜索用时 0 毫秒
61.
Helene Chapy Sylvie Klieber Priscilla Brun Sabine Gerbal‐Chaloin Xavier Boulenc Olivier Nicolas 《Biopharmaceutics & drug disposition》2015,36(8):491-506
Physiological based pharmacokinetic (PBPK) modeling is now commonly used in drug development to integrate human or animal physiological data in order to predict pharmacokinetic profiles. The aim of this work was to construct and refine a PBPK model of irbesartan taking into account its active uptake via OATP1B1/B3 in order to predict more accurately its pharmacokinetic profile using Simcyp®. The activity and expression of the human hepatocyte transporters OATP1B1 and OATP1B3 were studied. The relative activity factors (RAFs) for OATP1B1 and OATP1B3 transporters were calculated from intrinsic clearances obtained by concentration dependent uptake experiments in human hepatocytes and HEK overexpressing cells: RAF1B1 using estrone‐3‐sulfate and pitavastatine clearances, and RAF1B3 using cholecystokinine octapeptide (CCK‐8) clearances. The relative expression factor (REF) was calculated by comparing immunoblotting of hepatocytes (REFHH) or tissues (REFtissue) with those of overexpressing HEK cells for each transporter. These scaling factors were applied in a PBPK model of irbesartan using the Simcyp® simulator. Pharmacokinetic simulation using REFHH (1.82 for OATP1B1, 8.03 for OATP1B3) as an extrapolation factor was the closest to the human clinical pharmacokinetic profile of irbesartan. These investigations show the importance of integrating the contribution of the active uptake of a drug in the liver to improve PBPK modeling. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
62.
63.
Nathan J Kolla Brittany Matthews Alan A Wilson Sylvain Houle R Michael Bagby Paul Links Alexander I Simpson Amina Hussain Jeffrey H Meyer 《Neuropsychopharmacology》2015,40(11):2596-2603
Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [11C] harmine PET to measure MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=−0.50 to −0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity. 相似文献
64.
65.
Nørrelund H Frystyk J Jørgensen JO Møller N Christiansen JS Ørskov H Flyvbjerg A 《The Journal of clinical endocrinology and metabolism》2003,88(7):3292-3298
The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity. 相似文献
66.
Paul S. Nabity PhD Carlos A. Jaramillo MD PhD Patricia A. Resick PhD Cindy A. McGeary PhD Blessen C. Eapen MD Casey L. Straud PsyD Willie J. Hale PhD Timothy T. Houle PhD Brett T. Litz PhD Jim Mintz PhD Donald B. Penzien PhD Stacey Young-McCaughan RN PhD Terence M. Keane PhD Alan L. Peterson PhD Donald D. McGeary PhD Consortium to Alleviate PTSD 《Headache》2021,61(9):1334-1341
67.
Eva M. Sturm Kimberly D. Dyer Caroline M. Percopo Akos Heinemann Helene F. Rosenberg 《European journal of immunology》2013,43(8):2217-2228
Here, we describe a novel method via which ex vivo cultured mouse bone marrow derived eosinophils (bmEos) can be adoptively transferred into recipient mice in order to study receptor‐dependent recruitment to lung tissue in vivo. Intratracheal instillation of recombinant human eotaxin‐2 (hCCL24) prior to introduction of bmEos via tail vein injection resulted in an approximately fourfold increase in Siglec F‐positive/CD11c‐negative eosinophils in the lungs of eosinophil‐deficient ΔdblGATA recipient mice compared with controls. As anticipated, bmEos generated from CCR3‐gene‐deleted mice did not migrate to the lung in response to hCCL24 in this model, indicating specific receptor dependence. BmEos generated from GFP‐positive BALB/c mice responded similarly to hCCL24 in vitro and were detected in lung tissue of BALB/c WT as well as BALB/c ΔdblGATA eosinophil‐deficient recipient mice, at approximately fourfold (at 5 h post‐injection) and approximately threefold (at 24 h postinjection) over baseline, respectively. Comparable results were obtained with GFP‐positive C57BL/6 bmEos responding to intratracheal hCCL24 in C57BL/6 ΔdblGATA recipient mice. The use of ex vivo cultured bmEos via one or more of these methods offers the possibility of manipulating bmEos prior to transfer into a WT or gene‐deleted recipient host. Thus, this chemotaxis model represents a novel and robust tool for pharmacological studies in vivo. 相似文献
68.
69.
70.
Solriamfetol for Excessive Daytime Sleepiness in Parkinson's Disease: Phase 2 Proof-of-Concept Trial