全文获取类型
收费全文 | 3579篇 |
免费 | 190篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 69篇 |
儿科学 | 127篇 |
妇产科学 | 52篇 |
基础医学 | 538篇 |
口腔科学 | 90篇 |
临床医学 | 191篇 |
内科学 | 633篇 |
皮肤病学 | 63篇 |
神经病学 | 276篇 |
特种医学 | 229篇 |
外科学 | 424篇 |
综合类 | 58篇 |
预防医学 | 357篇 |
眼科学 | 83篇 |
药学 | 327篇 |
中国医学 | 8篇 |
肿瘤学 | 256篇 |
出版年
2023年 | 21篇 |
2022年 | 14篇 |
2021年 | 65篇 |
2020年 | 41篇 |
2019年 | 77篇 |
2018年 | 80篇 |
2017年 | 80篇 |
2016年 | 84篇 |
2015年 | 83篇 |
2014年 | 129篇 |
2013年 | 144篇 |
2012年 | 257篇 |
2011年 | 238篇 |
2010年 | 135篇 |
2009年 | 113篇 |
2008年 | 194篇 |
2007年 | 188篇 |
2006年 | 217篇 |
2005年 | 201篇 |
2004年 | 159篇 |
2003年 | 152篇 |
2002年 | 119篇 |
2001年 | 67篇 |
2000年 | 62篇 |
1999年 | 58篇 |
1998年 | 18篇 |
1994年 | 14篇 |
1993年 | 16篇 |
1992年 | 51篇 |
1991年 | 43篇 |
1990年 | 47篇 |
1989年 | 48篇 |
1988年 | 38篇 |
1987年 | 35篇 |
1986年 | 30篇 |
1985年 | 21篇 |
1984年 | 26篇 |
1983年 | 20篇 |
1979年 | 25篇 |
1977年 | 18篇 |
1975年 | 16篇 |
1974年 | 18篇 |
1973年 | 20篇 |
1972年 | 18篇 |
1971年 | 21篇 |
1970年 | 21篇 |
1968年 | 15篇 |
1967年 | 20篇 |
1966年 | 17篇 |
1933年 | 13篇 |
排序方式: 共有3781条查询结果,搜索用时 15 毫秒
61.
Julie?A.?McCarronEmail author Sandrine?Marchais-Oberwinkler Victor?W.?Pike Jari?Tarkiainen Christer?Halldin Judit?Sóvagó Balàzs?Gulyas Hakan?V.?Wikstr?m Lars?Farde 《Molecular imaging and biology》2005,7(3):209-219
PURPOSE: [carbonyl-11C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl)-N-pyridinyl)cyclohexanecarboxamide ([carbonyl-11C]WAY-100635) is an effective radioligand for imaging brain 5-HT1A receptors with positron emission tomography (PET). However, this radioligand has some drawbacks for deriving relative regional receptor densities, including rapid metabolism, which acts against accurate definition of an arterial input function for compartmental modeling, and very low nonspecific binding in brain, which detracts from the accuracy of modeling by a simplified reference tissue (cerebellum) approach. Here, in a search for a radioligand that overcomes these limitations, we investigated the effects of introducing a single methyl group at either of the carbon atoms alpha to the amide bond in [11C]WAY-100635. PROCEDURES: Ligands with a methyl group on the alpha carbon of the cyclohexyl group (SWAY) or the alpha carbon of the C2H4 linker ((R,S)-JWAY) were synthesized and tested for binding affinity and intrinsic activity at 5-HT1A receptors. SWAY was labeled with carbon-11 (t1/2 = 20.4 minutes; beta+ = 99.8%) in its O-methyl group and (R,S)-JWAY in its carbonyl group. Each radioligand was evaluated by PET experiments in cynomolgus monkey. RESULTS: SWAY and (R,S)-JWAY were found to be high-affinity antagonists at 5-HT1A receptors. After injection of [11C]SWAY into monkey, radioactivity uptake in brain reached a maximum of 3% at 4.5 minutes and decreased to 0.7% at 72 minutes. However, over the time span of the experiment, radioactivity concentrations in 5-HT1A receptor-rich brain regions were only fractionally higher than in cerebellum. Radioactivity represented by parent radioligand in plasma was 39% at 45 minutes. After injection of [11C](R,S)-JWAY alone, radioactivity uptake in brain reached a maximum of 4.8% at 2.5 minutes and decreased to 1.2% at 90 minutes. At this time, radioactivity concentration in 5-HT1A receptor-rich brain regions was markedly greater than in cerebellum. In another PET experiment, the monkey was predosed with WAY-100635 before [11C](R,S)-JWAY injection. At 90 minutes after injection, the ratio of radioactivity in 5-HT1A receptor-rich regions to that in cerebellum was reduced to near unity. Radioactivity represented by parent radioligand in plasma was 12% at 45 minutes. CONCLUSIONS: [11C](R,S)-JWAY, but not [11C]SWAY, gives a sizeable 5-HT1A receptor-selective PET signal in monkey. The presence of a C-methyl group adjacent to the amide bond in SWAY or (R,S)-JWAY fails to counter metabolism. 相似文献
62.
63.
64.
65.
66.
Pierson ME Andersson J Nyberg S McCarthy DJ Finnema SJ Varnäs K Takano A Karlsson P Gulyás B Medd AM Lee CM Powell ME Heys JR Potts W Seneca N Mrzljak L Farde L Halldin C 《NeuroImage》2008,41(3):1075-1085
The 5-HT1B receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. Here we report the synthesis of a novel PET radioligand, [11C]AZ10419369 (5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide), for in vivo visualization of 5-HT1B receptors in the brains of macaques and humans subjects. [11C]AZ10419369 was prepared by N-methylation of (8-(1-piperazinyl)-5-methylchrom-2-en-4-one-2-(4-morpholinophenyl) carboxamide, using carbon-11 methyl triflate. Regional brain uptake patterns of [11C]AZ10419369 were characterized by PET measurements in two macaques and a preliminary study in two human subjects. In addition, AZ10419369 was prepared in tritium labeled form for in vitro autoradiography studies in macaque brain tissue sections. The radiochemical purity of [11C]AZ10419369 was >99% and specific radioactivity was >3600 Ci/mmol. After iv injection of [11C]AZ10419369, 3-4% was in brain after 7.5 min. The regional brain distribution of radioactivity was similar in humans and macaques showing the highest uptake of radioactivity in the occipital cortex and the basal ganglia, in accord with autoradiographic studies performed using [3H]AZ10419369. Uptake was moderate in the temporal and frontal cortical regions, lower in the thalamus and lowest in the cerebellum. In macaques pre-treated with the selective 5-HT1B receptor antagonist, AR-A000002, binding was reduced in a dose-dependent manner, consistent with specific binding to 5-HT1B receptors. These data support [11C]AZ10419369 as a suitable radioligand for labeling 5-HT1B receptors in the primate brain. This radioligand may be useful in future studies evaluating drug-induced receptor occupancy and measurement of brain 5-HT1B receptor levels in patients with psychiatric disorders. 相似文献
67.
Increased microvascular permeability resulting in tissue edema is a hallmark of sepsis-related microcirculatory failure, and
leukocyte–endothelium interaction is thought to assume major importance in this context. However, the role of nitric oxide
(NO) in the interplay of inflammation, leukocyte–endothelium interaction and increased microcirculatory permeability is still
a matter of debate. Hollenberg et al. now report, in the previous issue of Critical Care, that neither genetic deletion nor pharmacologic blockade of the inducible isoform of the NO synthase (iNOS) affected the
sepsis-related aggravation of leukocyte rolling and adhesion, whereas iNOS inhibition attenuated microvascular permeability.
The authors conclude that excess NO resulting from iNOS activation is important in modulating vascular permeability during
sepsis, but that this effect is independent of its action on leukocytes. 相似文献
68.
69.
70.