全文获取类型
收费全文 | 213篇 |
免费 | 6篇 |
国内免费 | 4篇 |
专业分类
基础医学 | 15篇 |
临床医学 | 15篇 |
内科学 | 16篇 |
神经病学 | 3篇 |
特种医学 | 2篇 |
外科学 | 3篇 |
综合类 | 77篇 |
预防医学 | 42篇 |
眼科学 | 1篇 |
药学 | 35篇 |
中国医学 | 8篇 |
肿瘤学 | 6篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 11篇 |
2013年 | 12篇 |
2012年 | 8篇 |
2011年 | 25篇 |
2010年 | 11篇 |
2009年 | 21篇 |
2008年 | 16篇 |
2007年 | 17篇 |
2006年 | 18篇 |
2005年 | 10篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有223条查询结果,搜索用时 15 毫秒
81.
82.
Kazuya Hosokawa Tomoko Ohnishi Naoki Miura Hisayo Sameshima Takehiko Koide Kenichi A. Tanaka Ikuro Maruyama 《Thrombosis research》2014
Introduction
Thrombin-mediated activation of human platelets involves the G-protein-coupled protease-activated receptors PAR1 and PAR4. Inhibition of PAR1 and/or PAR4 is thought to modulate platelet activation and subsequent procoagulant reactions. However, the antithrombotic effects of PAR1 and PAR4 antagonism have not been fully elucidated, particularly under flow conditions.Materials and Methods
A microchip-based flow chamber system was used to evaluate the influence of SCH79797 (PAR1 antagonist) and YD-3 (PAR4 antagonist) on thrombus formation mediated by collagen and tissue thromboplastin at shear rates simulating those experienced in small- to medium-sized arteries (600 s- 1) and large arteries and small veins (240 s- 1).Results
At a shear rate of 600 s- 1, SCH79797 (10 μM) efficiently reduced fibrin-rich platelet thrombi and significantly delayed occlusion of the flow chamber capillary (1.44 fold of control; P < 0.001). The inhibitory activity of SCH79797 was diminished at 240 s- 1. YD-3 (20 μM) had no significant effect at either shear rate. The antithrombotic effects of SCH79797 were significantly augmented when combined with aspirin and AR-C66096 (P2Y12 antagonist), but not with YD-3. In contrast, no significant inhibition of tissue factor-induced clot formation under static conditions was observed in blood treated with SCH79797 and YD-3, although thrombin generation in platelet-rich plasma was weakly delayed by these antagonists.Conclusions
Our results suggest that the antithrombotic activities of PAR1 and/or PAR4 antagonism is influenced by shear conditions as well as by combined platelet inhibition with aspirin and a P2Y12-antagonist. 相似文献83.
文章将Flash与Access数据库结合,通过数据库中的数据来实时控制Flash动画的变动,实现Flash与数据库的互动,并将其应用于疾病统计和分析。Flash不能直接与数据库进行通信,以ASP为中间语言,将数据库数据生成XML树格式的数据文件,再利用ActionScript3.0脚本语言解析XML树格式的数据文件,从而实现与数据库的通信。 相似文献
84.
Today, cardiovascular diseases (CVD) remain the principal cause of death in industrialized countries and are linked to obesity and metabolic syndrome. Metabolic syndrome is characterized by changes in arterial blood pressure, glucose metabolism, lipid and lipoprotein profiles in addition to inflammation. Adipose tissue produces many cytokines and secretory factors termed adipokines. Intra-abdominal (visceral) adipose tissue in particular, rather than peripheral, appears to be associated with global cardiometabolic risk. The present article summarizes information on five recently discovered adipokines: vaspin, visfatin, apelin, acylation stimulating protein (ASP) and retinol-binding protein 4 (RBP4) and their potential beneficial or deleterious roles in obesity and atherosclerosis. Vaspin may have antiatherogenic effects through its potential insulin-sensitizing properties. Similarly, visfatin has been suggested to enhance insulin sensitivity, but its potential role in plaque destabilization may counteract this. Apelin, via inhibition of food intake, and increases in physical activity and body temperature, may promote weight loss, resulting in a beneficial antiatherogenic effect. Further, favourable effects on vasodilatation and blood pressure add to this positive effect. Considering its increased levels in subjects with demonstrated atherosclerosis, RBP4 may constitute a biomarker. Lastly, ASP, often increased in obesity and metabolic disorders, may be contributing to efficient lipid storage, and decreasing or blocking ASP may provide a potential antiobesity target. Adipokines may further contribute to obesity-atherosclerosis relationships, the full understanding of which will require further research. 相似文献
85.
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(9):757-765
Abstract1.?Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice).2.?Rat biological samples collected after oral dosing of 14C-labelled ASP015K were examined using a liquid chromatography–radiometric detector and mass spectrometer (LC–RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC–MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance.3.?Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates. 相似文献
86.
《Expert opinion on therapeutic targets》2013,17(1):119-134
The prevalence of obesity is increasing rapidly in most parts of the world and effective therapeutic drugs are urgently needed. The discovery of leptin in 1994 initiated a new understanding of adipose tissue function, and adipose tissue is now known to not only store and release fatty acids, but also to produce a wealth of factors that have an impact on the regulation of body weight and blood glucose homeostasis. Also, adipocytes express proteins that engage signalling pathways playing important roles in fuel substrate and energy metabolism. These proteins constitute a diverse array of adipose target candidates for the development of drugs to treat obesity. Some of these potential targets have been validated and are now in drug development stages, providing hope that the current obesity epidemic can be addressed by effective drug treatments in the near future. 相似文献
87.
Kobayashi M Kubo S Iwata M Ohtsu Y Takahashi K Shimizu Y 《International immunopharmacology》2011,11(6):732-739
We investigated the pharmacology of a novel phosphodiesterase (PDE) 4 inhibitor, ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), comparing its potency with that of the most advanced PDE4 inhibitors, roflumilast and cilomilast. PDE4 inhibition by ASP3258 (IC(50)=0.28nM) was as potent as that achieved with roflumilast. ASP3258 inhibited lipopolysaccharide-induced tumor necrosis factor (TNF)-α production in rat whole blood cells (IC(50)=8.8 nM) and rat alveolar macrophages (IC(50)=2.6 nM). Orally administered ASP3258, roflumilast, and cilomilast dose-dependently inhibited production of interleukin-4, TNF-α, and cysteinyl leukotrienes, as well as leukocyte infiltration in bronchoalveolar lavage fluid from the airways of ovalbumin-sensitized Brown Norway rats, and these compounds showed almost complete inhibition at doses of 3, 3, and 30 mg/kg, respectively. PDE4 inhibitors induce emesis by mimicking the pharmacological action of α(2)-adrenoceptor antagonist. However, orally administered roflumilast (3mg/kg) and cilomilast (10mg/kg), but not ASP3258 (3mg/kg), inhibited α(2)-adrenoceptor agonist-induced anesthesia in rats and induced emesis in ferrets. Although ASP3258 (3mg/kg) inhibited airway inflammation completely, it had no emetic activity. As such, this compound may be useful in treating airway inflammatory diseases such as asthma and COPD. 相似文献
88.
当归多糖对小鼠化学性肝损伤抗氧化酶及一氧化氮含量的影响 总被引:1,自引:0,他引:1
[目的]探讨当归多糖(angelica sinensis polysaccharide ASP)对CCL4肝损伤小鼠抗氧化酶、自由基和一氧化氮(nitric oxide,NO)的含量的影响。[方法]以4月龄昆明种小鼠为研究对象,分对照组、模型组和高、中、低当归多糖干预组,各组均给予常规饲料,自由饮水;干预组每天按体重用不同浓度的当归多糖灌胃,饲养7d,末次灌胃2h,正常对照组腹腔注射调和油溶液,其余各组腹腔注射0.15%CCl4调和油溶液,24h眼球取血,分离血清测ALT、AST。处死小鼠取出肝脏计算肝体指数,制备肝匀浆测定SOD、NOS活性和MDA及NO的含量。[结果]与模型组比较当归多糖能减轻化学性肝损伤小鼠炎性反应,降低MDA的含量(P﹤0.01)、增加SOD的活性(P﹤0.05~0.01),抑制NOS的活性和NO的含量(P﹤0.05~0.01)。[结论]当归多糖对CCL4肝损伤有保护作用。 相似文献
89.
90.
目的:探究FLT3急性髓细胞性白血病(acute myeloid leukemia, AML)抑制剂ASP2215联合组蛋白去乙酰化酶(histone deacetylase inhibitor,HDAC)抑制剂SAHA,对伴FLT3-ITD突变的细胞株MV4-11的协同作用及其作用机制。方法:用不同浓度的ASP2215、SAHA单药或两药联合处理白血病细胞株MV4-11,观察细胞形态变化,采用CCK-8试剂盒检测其细胞活力,用流式细胞仪检测细胞凋亡率,蛋白免疫印迹检测FLT3及下游信号分子STAT5的磷酸化,分析凋亡调控蛋白Mcl-1、Bcl-xL、Bcl-2、Bax和caspase-9、caspase-3的蛋白含量。结果:①相较于FLT3野生型细胞株THP-1,ASP2215能够特异性地抑制FLT3-ITD突变AML细胞株MV4-11细胞的增殖。②ASP2215和SAHA单药处理均能抑制MV4-11细胞的活性,这种抑制作用呈浓度和时间依赖性,且两药联合使用时能够协同抑制MV4-11细胞株的活性,不同药物浓度联合的联合指数(combination index,CI)值皆小于1。③ASP2215和SAHA呈浓度和时间依赖性诱导MV4-11细胞凋亡,两者联合能够进一步增加MV4-11细胞凋亡。MV4-11细胞凋亡的过程中,伴caspase-3和caspase-9蛋白剪切活化,且活化程度随细胞凋亡增加而上升。相较于单药作用,两药联合能够引起更多的caspase-3和caspase-9剪切活化。形态学上,细胞凋亡和坏死改变随着药物浓度增加依次增多,且两药物联合能够引起细胞更明显的凋亡和坏死改变。④FLT3抑制剂ASP2215能够降低FLT3受体及下游分子STAT5的磷酸化水平,SAHA对FLT3及下游STAT5分子磷酸化也有轻度抑制作用。ASP2215和SAHA都能引起Mcl-1和Bcl-xL抗凋亡蛋白水平的降低,轻度下调Bcl-2蛋白和轻度上调Bax蛋白表达水平。两药联合相较于单药能够进一步下调Mcl-1、Bcl-xL的蛋白表达水平和Bcl-2/Bax蛋白比例。结论:ASP2215联合SAHA能够协同抑制伴FLT3-ITD突变MV4-11细胞株增殖,促进细胞凋亡,其机制涉及两药对FLT3-STAT5通路不同程度抑制作用,以及对凋亡相关蛋白Mcl-1、Bcl-xL及Bcl-2/Bax蛋白比例的调控。 相似文献