全文获取类型
收费全文 | 597篇 |
免费 | 24篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 18篇 |
妇产科学 | 5篇 |
基础医学 | 85篇 |
口腔科学 | 6篇 |
临床医学 | 30篇 |
内科学 | 68篇 |
皮肤病学 | 3篇 |
神经病学 | 31篇 |
特种医学 | 4篇 |
外科学 | 35篇 |
综合类 | 68篇 |
预防医学 | 19篇 |
药学 | 106篇 |
中国医学 | 7篇 |
肿瘤学 | 142篇 |
出版年
2024年 | 1篇 |
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 4篇 |
2015年 | 15篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 21篇 |
2011年 | 29篇 |
2010年 | 26篇 |
2009年 | 19篇 |
2008年 | 29篇 |
2007年 | 51篇 |
2006年 | 38篇 |
2005年 | 33篇 |
2004年 | 31篇 |
2003年 | 24篇 |
2002年 | 23篇 |
2001年 | 22篇 |
2000年 | 18篇 |
1999年 | 17篇 |
1998年 | 9篇 |
1997年 | 12篇 |
1996年 | 6篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 9篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 9篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有630条查询结果,搜索用时 31 毫秒
61.
Shao-yu WU Guang-fa WANG Zhong-qiu LIU in-jun RAO Lin Lü Wei XU Shu-guang WU Jia-jie ZHANG 《中国药理学报》2009,(2):202-208
Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase. Methods: Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol (TC) and triglyceride (TG) levels were measured using LabassayTM kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes. Results: Geniposide (200 and 400 mg/kg) significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity. Conclusion: Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities. 相似文献
62.
目的:研究血小板衍化内皮细胞生长因子(TP/PD-ECGF)在胃癌中的表达及血小板增多情况,并对其与胃癌患者临床病理特征和预后的关系进行探讨。方法:采用免疫组化EnVision两步法检测107例胃癌组织中TP/PD-ECGF的表达,记录血小板增多情况,并分析二者与胃癌患者临床病理特征及预后的关系。结果:胃癌患者中TP/PD-ECGF阳性表达率为71.0%,与血小板增多呈正相关(P〈0.01)。TP/PD-ECGF表达、血小板增多与肿瘤分期、淋巴结转移、远处转移及分化程度呈正相关。TP/PD-ECGF阳性与阴性表达患者3年、5年总生存率分别为69.04%、18.12%和88.87%、75.20%,二者差异有统计学意义(P=0.0383);3年、5年无进展生存率分别为64.87%、17.92%和82.73%、35.00%,二者差异有统计学意义(P=0.0350)。Cox比例风险模型多因素分析显示,肿瘤分期、淋巴结转移、远处转移、TP/PD-ECGF及血小板增多均是影响胃癌预后独立的危险因素。结论:TP/PD-ECGF表达与血小板增多呈正相关,二者与胃癌生长和浸润转移关系密切,可作为胃癌独立的预后因素。 相似文献
63.
A novel inhibitor of Schistosoma PNP was identified using an “in silico” approach allied to enzyme inhibition assays. The compound has a monocyclic structure which has not been previously described for PNP inhibitors. The crystallographic structure of the complex was determined and used to elucidate the binding mode within the active site. Furthermore, the predicted pose was very similar to that determined crystallographically, validating the methodology. The compound Sm_VS1, despite its low molecular weight, possesses an IC50 of 1.3 μM, surprisingly low when compared with purine analogues. This is presumably due to the formation of eight hydrogen bonds with key residues in the active site E203, N245 and T244. The results of this study highlight the importance of the use of multiple conformations for the target during virtual screening. Indeed the Sm_VS1 compound was only identified after flipping the N245 side chain. It is expected that the structure will be of use in the development of new highly active non-purine based compounds against the Schistosoma enzyme. 相似文献
64.
Reduction of the pentavalent arsenate (AsV) to the thiol-reactive arsenite (AsIII) toxifies this environmentally prevalent form of arsenic, yet its biochemical mechanism in mammals is incompletely understood. Purine nucleoside phosphorylase (PNP) has been shown recently to function as an AsV reductase in vitro, provided its substrate (inosine or guanosine) and an appropriate dithiol (e.g., dithiothreitol, DTT) were present. It was of interest to know if this ubiquitous enzyme played a significant role in reduction of AsV to AsIII in vivo. Two approaches were used to test this. First, it was determined if compounds that influenced AsV reduction by purified PNP (i.e., nucleosides, thiols, and PNP inhibitors) would similarly affect reduction of AsV by human erythrocytes. Erythrocytes were incubated with AsV, and the formed AsIII was quantified by HPLC-hydride generation-atomic fluorescence spectrometry. The red blood cells reduced AsV at a considerable rate, which could be enhanced by inosine or inosine plus DTT. These stimulated AsIII formation rates were PNP-dependent, as PNP inhibitors strongly inhibited them. In contrast, PNP inhibitors had little if any inhibitory effect on AsIII formation in the absence of exogenous inosine, indicating that this basal rate of AsV reduction is PNP-independent. Second, the role of PNP in reduction of AsV in vivo was also assessed by investigating the effect of the PNP inhibitor BCX-1777 on the biotransformation of AsV in control and DTT-treated rats with cannulated bile duct and ligated renal pedicles. Although it abolished hepatic PNP activity, BCX-1777 influenced neither the biliary excretion of AsIII and monomethylarsonous acid, nor the tissue concentration of AsV and its metabolites in either group of AsV-injected rats. Thus, despite its in vitro activity, PNP does not appear to play a significant role in AsV reduction in human erythrocytes and in rats in vivo. Further research should clarify the in vivo relevant mechanisms of AsV reduction in mammals. 相似文献
65.
66.
67.
Pentacyclic Triterpenoids from Spikes of Prunella vulgaris L. Inhibit Glycogen Phosphorylase and Improve Insulin Sensitivity in 3T3‐L1 Adipocytes 下载免费PDF全文
Phytochemical investigation of methanol extract from the spikes of Prunella vulgaris L. led to the isolation of two new pentacyclic triterpenoid glycosides Vulgasides I (1) and II (2) along with 13 known compounds (3–15). Their structures were established on the basis of nuclear magnetic resonance (1D and 2D) and mass spectroscopic data analysis. All the isolated compounds were screened for glycogen phosphorylase inhibitory activity and also evaluated for their effect on insulin sensitivity in 3T3‐L1 adipocytes. Two new compounds (1, 2) did not demonstrate the glycogen phosphorylase inhibitory activity, but other compounds (3–11) exhibited varying degrees of glycogen phosphorylase inhibitory activity with IC50 values in the range from 30.69 to 68.85 μM. Compounds 3, 6, 7, 11, and 13 demonstrated markedly increased insulin‐mediated glucose consumption in 3T3‐L1 adipocytes. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
68.
目的检测子宫内膜癌中胸苷磷酸化酶(TP)的表达情况,探讨它与子宫内膜癌预后的相关性及临床意义。方法采用免疫组化SP法检测15例正常内膜,10例不典型增生内膜,48例子宫内膜癌石蜡标本中的TP蛋白表达情况。结果子宫内膜癌TP表达显著高于正常内膜(PTP=0.029)。TP表达与肿瘤分化程度、浸润深度、淋巴结转移及临床病理分期无相关性(P>0.05)。结论 TP的过度表达可能与子宫内膜癌的预后有关。 相似文献
69.
Summary The role of fetal insulin in placental glycogen accumulation, which occurs despite insulin deficiency in maternal diabetes, was studied in rats. Streptozotocin was injected into fetuses of non-diabetic and streptozotocin-diabetic mothers on days 19.5 and 20.5 of gestation, causing fetal hypoinsulinaemia and pancreatic insulin depletion. Placental glycogen content of either 1.6 mg/g in non-diabetic rats or 6.5 mg/g in diabetic rats was not affected by fetal streptozotocin treatment. Glycogen distribution was also measured in the placenta to assess the effect of fetal hypoinsulinaemia on glycogen content in its fetal segment. The glycogen concentration ratio between the fetal and maternal segments in diabetic rats was 0.3 and increased to 0.5 in diabetic rats, without being affected by fetal hypoinsulinaemia. There was no significant effect of fetal hypoinsulinaemia on the activities of placental glycogen synthase or glycogen phosphorylase, both in nondiabetic and diabetic rats. Fetal hypoinsulinaemia was associated, however, with a marked decrease in fetal liver glycogen together with a decrease in fetal liver weight, which was more pronounced than the decrease in fetal body weight. Administration of insulin to the streptozotocin-treated fetuses restored the impaired glycogen synthesis (measured by incorporation of U-[14C]-glucose and 3H2O in the fetal liver) without affecting glycogen synthesis in the placenta. These results demonstrate: (1) placental glycogen metabolism in contrast to fetal liver glycogen metabolism, is not regulated by fetal insulin; (2) the reduced fetal liver weight and its glycogen content, rather than hyperglycaemia, are the salient features of fetal insulin deficiency; and (3) placental glycogen accumulation in diabetes is related to the hyperglycaemia of maternal origin and not to the changes in maternal or fetal insulin availability. 相似文献
70.