首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2204篇
  免费   119篇
  国内免费   22篇
  2024年   2篇
  2023年   18篇
  2022年   24篇
  2021年   29篇
  2020年   46篇
  2019年   39篇
  2018年   44篇
  2017年   42篇
  2016年   40篇
  2015年   67篇
  2014年   178篇
  2013年   135篇
  2012年   144篇
  2011年   196篇
  2010年   123篇
  2009年   113篇
  2008年   128篇
  2007年   120篇
  2006年   120篇
  2005年   93篇
  2004年   91篇
  2003年   86篇
  2002年   49篇
  2001年   15篇
  2000年   18篇
  1999年   16篇
  1998年   9篇
  1997年   11篇
  1996年   21篇
  1995年   23篇
  1994年   18篇
  1993年   15篇
  1992年   25篇
  1991年   18篇
  1990年   8篇
  1989年   11篇
  1988年   12篇
  1987年   10篇
  1986年   14篇
  1985年   18篇
  1984年   41篇
  1983年   23篇
  1982年   31篇
  1981年   22篇
  1980年   10篇
  1979年   14篇
  1978年   3篇
  1977年   6篇
  1976年   2篇
  1972年   2篇
排序方式: 共有2345条查询结果,搜索用时 15 毫秒
1.
We describe a solid vegetable oil–water gel structure which is stabilized through the use of low concentrations of monoglycerides, containing no added trans fats or saturated fats. The resulting structure consists of oil droplets encapsulated in self-assembled crystalline monoglyceride multilayers, surrounded by a continuous water phase. Acute ingestion human feeding trials indicated that the serum triglyceride loading was significantly lower after ingestion of the structured gel rather than a simple oil–water mixture, resulting in an attenuated increase in serum insulin. This indicates the effectiveness of encapsulation in modulating blood lipid and insulin response in humans, and suggests a strategy that can be employed for the controlled release of food macronutrients. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.  相似文献   
2.
3.
We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 13, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure–activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner.  相似文献   
4.
目的:探讨短期胰岛素泵强化治疗对2型糖尿病患者血脂血糖代谢的影响。方法:选取76例2型糖尿病患者,按给药方式不同分为两组,对照组(38例)给予门冬胰岛素常规治疗,观察组(38例)给予胰岛素泵强化治疗,依据两组治疗前后的血糖、血脂指标变化及治疗前、治疗后1周、2周的ADL量表评分评价短期胰岛素泵强化治疗对2型糖尿病患者血脂血糖代谢的影响。结果:治疗后,两组患者的空腹血糖(FPG)、糖化血红蛋白(Hb Alc)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前显著降低,高密度脂蛋白胆固醇(HDL-C)水平均明显升高,且观察组FPG、Hb Alc、TC、TG、LDL-C水平均明显低于对照组,HDL-C水平显著高于对照组(P0.05)。治疗后1周、2周,两组ADL评分均较治疗前明显提高,且观察组显著高于对照组(P0.05)。结论:短期胰岛素泵强化治疗能显著改善2型糖尿病患者的血糖血脂代谢紊乱,并提高患者的日常生活能力。  相似文献   
5.
Three principally different sites of action have been reported for proinsulin C-peptide, at surface-mediated, intracellular, and extracellular locations. Following up on the latter, we now find that (i) mass spectrometric analyses reveal the presence of the C-peptide monomer in apparent equilibrium with a low-yield set of oligomers in weakly acidic or basic aqueous solutions, even at low peptide concentrations (sub-μM). It further shows not only C-peptide to interact with insulin oligomers (known before), but also the other way around. (ii) Polyacrylamide gel electrophoresis of C-peptide shows detectable oligomers upon Western blotting. Formation of thioflavin T positive material was also detected. (iii) Cleavage patterns of analogues are compatible with C-peptide as a substrate of insulin degrading enzyme. Combined, the results demonstrate three links with insulin properties, in a manner reminiscent of amyloidogenic peptides and their chaperons in other systems. If so, peripheral C-peptide/insulin interactions, absolute amounts of both peptides and their ratios may be relevant to consider in diabetic and associated diseases.  相似文献   
6.
7.
目的观察不同时间脂肪乳输注使血浆游离脂肪酸(FFA)升高对大鼠葡萄糖输注率(GIR)的影响。方法分别给大鼠输注脂肪乳2、5、7和48 h,行高胰岛素-正血糖钳夹试验评价葡萄糖输注率,测定血浆葡萄糖、FFA。结果与生理盐水输注组比较,2 h脂肪乳输注使血浆FFA升高了2倍(P〈0.01),GIR下降27%(P〈0.05),脂肪乳输注5 h GIR降低了52%(P〈0.01),7 h GIR降低56%(P〈0.01),输注48 h脂肪乳GIR降低58%(P〈0.01),5 h组7、h组及48 h脂肪乳输注组间GIR差异没有统计学意义。结论大鼠输注脂肪乳使FFA浓度达到基础值的3倍左右,可复制出脂毒性胰岛素抵抗的模型,而且胰岛素抵抗达到一定程度后保持恒定。  相似文献   
8.
Oral administration of peptide and protein drugs faces a big challenge partly due to the hostile gastrointestinal (GI) environment. Lipid-based delivery systems are attractive because they offer some protection for peptides and proteins. In this context, we prepared a special lipid-based oral delivery system: archaeosomes, made of the polar lipid fraction E (PLFE) extracted from Sulfolobus acidocaldarius, and explored its potential as an oral drug delivery vehicle. Our study demonstrates that archaeosomes have superior stability in simulated GI fluids, and enable fluorescent labeled peptides to reside for longer periods in the GI tract after oral administration. Although archaeosomes have little effect on the transport of insulin across the Caco-2 cell monolayers, the in vivo experiments indicated that archaeosomes containing insulin induced lower levels of blood glucose than a conventional liposome formulation. These data indicate that archaeosomes could be a potential carrier for effective oral delivery of peptide drugs.  相似文献   
9.
10.
Chronic oxidative stress results in decreased responsiveness to insulin, eventually leading to diabetes and cardiovascular disease. Activation of the JNK signaling pathway can mediate many of the effects of stress on insulin resistance through inhibitory phosphorylation of insulin receptor substrate 1. By contrast, exercise, which acutely increases oxidative stress in the muscle, improves insulin sensitivity and glucose tolerance in patients with Type 2 diabetes. To elucidate the mechanism underlying the contrasting effects of acute versus chronic oxidative stress on insulin sensitivity, we used a cellular model of insulin-resistant muscle to induce either chronic or acute oxidative stress and investigate their effects on insulin and JNK signaling. Chronic oxidative stress resulted in increased levels of phosphorylated (activated) JNK in the cytoplasm, whereas acute oxidative stress led to redistribution of JNK-specific phosphatase MKP7 from the nucleus into the cytoplasm, reduction in cytoplasmic phospho-JNK, and a concurrent accumulation of phospho-JNK in the nucleus. Acute oxidative stress restored normal insulin sensitivity and glucose uptake in insulin-resistant muscle cells, and this effect was dependent on MKP7. We propose that the contrasting effects of acute and chronic stress on insulin sensitivity are driven by changes in subcellular distribution of MKP7 and activated JNK.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号