全文获取类型
收费全文 | 831篇 |
免费 | 96篇 |
国内免费 | 23篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 3篇 |
妇产科学 | 7篇 |
基础医学 | 70篇 |
口腔科学 | 12篇 |
临床医学 | 23篇 |
内科学 | 59篇 |
皮肤病学 | 10篇 |
神经病学 | 17篇 |
特种医学 | 6篇 |
外科学 | 28篇 |
综合类 | 130篇 |
预防医学 | 38篇 |
眼科学 | 8篇 |
药学 | 352篇 |
中国医学 | 124篇 |
肿瘤学 | 61篇 |
出版年
2024年 | 1篇 |
2023年 | 11篇 |
2022年 | 33篇 |
2021年 | 29篇 |
2020年 | 28篇 |
2019年 | 12篇 |
2018年 | 30篇 |
2017年 | 19篇 |
2016年 | 28篇 |
2015年 | 35篇 |
2014年 | 60篇 |
2013年 | 59篇 |
2012年 | 70篇 |
2011年 | 74篇 |
2010年 | 51篇 |
2009年 | 45篇 |
2008年 | 73篇 |
2007年 | 66篇 |
2006年 | 53篇 |
2005年 | 36篇 |
2004年 | 31篇 |
2003年 | 25篇 |
2002年 | 10篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1981年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有950条查询结果,搜索用时 15 毫秒
141.
The aim of this study was to investigate the effect of quercetin, a flavonoid, on the apoptotic pathway in a human prostate cell line (LNCaP). We observed that treatment of cells for 24h with quercetin-induced cell death in a dose-dependent manner. A sustained inhibition of the major survival signal, Akt, occurred in quercetin-treated cells. Treatment of LNCaP cells with an apoptosis inducing concentration of quercetin (100 microM) resulted in a rapid decrease in the inhibitory Ser473 phosphorylation of Akt leading to inhibition of its kinase activity. Quercetin treatment (100 microM) also caused a decrease in Ser136 phosphorylation of Bad, which is a downstream target of Akt. Protein interaction assay revealed that during treatment with quercetin, Bcl-xL dissociated from Bax and then associated with Bad. Our results also show that quercetin decreases the Bcl-xL:Bax ratio and increases translocation and multimerization of Bax to the mitochondrial membrane. The translocation is accompanied by cytochrome c release, and procaspases-3, -8 and -9 cleavage and increased poly(ADP-ribose) polymerase (PARP) cleavage. Similar results were observed in human colon cancer HCT116Bax+/+ cell line, but not HCT116Bax-/- cell line. Interestingly, at similar concentrations (100 microM), quercetin treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cell line (PrEC) and rat prostate epithelial cell line (YPEN-1). Our results indicate that the apoptotic processes caused by quercetin are mediated by the dissociation of Bax from Bcl-xL and the activation of caspase families in human prostate cancer cells. 相似文献
142.
目的:探讨槲皮素对糖尿病视网膜病变(DR)的保护作用及其抗氧化和抗炎机制。方法: 腹腔注射链脲佐菌素(STZ)建立小鼠糖尿病模型,随机分为正常对照组、造模组、槲皮素治疗组(n = 10)。治疗后定期监测小鼠精神状态、血糖、体重;检测小鼠视网膜结构变化、超氧化物歧化酶(SOD)活性、8-羟基脱氧鸟苷(8-OHdG)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-β(IL-β)的mRNA等水平。结果:与造模组相比,槲皮素降低小鼠血糖(P < 0.05),小鼠体重无明显差异(P > 0.05),视网膜细胞排列整齐,厚度增加;视网膜组织中8-OHdG、MDA、TNF-α mRNA、IL-6 mRNA、IL-β mRNA、Bax及p-p38 MAPK蛋白表达指数显著降低(P < 0.05),T-SOD活力和Bcl-2蛋白表达水平明显升高(P < 0.05),但各组p38 MAPK蛋白表达水平无明显差异(P > 0.05)。结论: 槲皮素改善2型糖尿病小鼠视网膜组织氧化应激损伤和炎症反应,其机制可能与p38 MAPK信号通路有关。 相似文献
143.
摘 要 目的:建立HPLC法测定姜黄素 槲皮素复方自微乳(CUR-QUE-SMEDDS)的载药量和包封率。方法: 采用离心法分离游离药物,HPLC法测定药物含量。色谱柱:Purospher STAR LP C18 柱(250 mm×4.6 mm,5 μm),流动相:乙腈 4%冰醋酸(50∶50),流速:1.0 ml·min-1,检测波长:370 nm,柱温:30℃,进样量:10 μl。结果: 姜黄素和槲皮素的线性范围分别为10.728~96.552 μg·mL-1(r=0.999 8)和1.08~9.72 μg·mL-1(r=0.999 9),平均回收率分别为99.98%(RSD=1.46%,n=9)和100.34%(RSD=1.06%,n=9)。CUR QUE SMEDDS中姜黄素和槲皮素的包封率分别为(95.97±0.50)% 和(95.91±2.52)%,载药量分别为(25.82±0.15)mg·g-1和(1.80±0.05)mg·g-1。结论:该法准确可靠,快速简便,适用于测定CUR-QUE-SMEDDS的载药量和包封率。 相似文献
144.
145.
槲皮素对LPS诱导中性粒细胞活性化效应的抑制作用 总被引:3,自引:2,他引:1
目的研究槲皮素(Quercetin,Que)对细菌脂多糖(Lipopolysaccharide,LPS)诱导的中性粒细胞(Polymorphonuclear,PMN)活化效应的影响。方法运用免疫荧光法和流式细胞术,对接受1h LPS刺激的PMN表面黏附分子(CD62L,CD11b/CD18)的表达进行测定,同时应用MTT法对不同状态下的PMN活性进行测定。结果Que对LPS诱导的中性粒细胞活化效应有明显抑制作用,表现为抑制细胞表面黏附分子CD62L的表达和促进CD11b/CD18的表达,同时Que对LPS增加细胞活性的效应有抑制作用。结论槲皮素通过对抗LPS对PMN黏附分子CD62L,CD11b/CD18的表达的影响,抑制LPS诱导的中性粒细胞活化效应,从而阻止PMN对血管内皮细胞的黏附,减少炎症细胞向炎症局灶的浸润,这可能是槲皮素发挥抗炎作用的一个重要机制。 相似文献
146.
目的探讨槲皮素对K562细胞的形态、血管内皮生长因子(VEGF)蛋白分泌和VEGF mRNA表达的影响.方法以K562细胞为研究对象,细胞形态学观察采用Wright's染色法;AnnecxinV标记检测细胞凋亡率;RT-PCR方法检测VEGF mRNA表达;ELISA法检测VEGF蛋白表达.结果1.经槲皮素处理后,细胞形态学上出现凋亡特征性改变;2.槲皮素处理后K562细胞凋亡率明显增加(P<0.01);3.槲皮素能下调K562细胞VEGF mRNA的表达(P<0.05);4.槲皮素处理后K562细胞显著降低VEGF蛋白的分泌(P<0.05).结论槲皮素在体外能抑制白血病细胞K562生长并诱导其凋亡;槲皮素可抑制白血病细胞分泌VEGF. 相似文献
147.
Sael Casas-Grajales Pablo Muriel 《World journal of gastrointestinal pharmacology and therapeutics》2015,6(3):59-72
Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals(FR).However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leadsto deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. 相似文献
148.
槲皮素恢复柔红霉素在白血病耐药细胞K562/ADM和HL-60/ADM中的分布 总被引:5,自引:1,他引:4
背景与目的:槲皮素是一种天然黄酮类中药成分,儿有多种生理活性,最近发现其有逆转白血病细胞耐药的作用,本研究旨在探讨槲皮素恢复柔红霉素在白血病耐药细胞的分布从而达到逆转耐药的机制:方法:通过MTT体外药敏法检测槲皮素对柔红霉素的增敏作用并确定逆转的浓度范围,作用于K562/ADM、HL-60/ADM细胞及相应敏感株K562和HL-60,借助激光共聚焦显微镜观察槲皮素怍用前后柔红霉素在亚细胞水平的分布变化:结果:20~40μmol/L槲皮素在体外能日月显提高柔红霉素对K562/ADM和HL-60/ADM的敏感性,恢复柔红霉素在亚细胞水平的分布,使其回归细胞核内,从而逆转多药耐药。结论:黄酬类中药槲皮素能够成为蒽环类药物治疗白血病中有效的化疗增敏剂。 相似文献
149.
Lee BH Choi SH Shin TJ Pyo MK Hwang SH Lee SM Paik HD Kim HC Nah SY 《European journal of pharmacology》2011,(1):79-85
Quercetin, one of the flavonoids, is a low molecular weight substance found in fruits and vegetables. Quercetin, like other flavonoids, has a wide range of neuropharmacological actions and antioxidant effects. The α9α10 nicotinic acetylcholine receptor is one of the numerous nicotinic acetylcholine receptors that exist as a heteropentameric form between efferent olivocochlear fibers and hair cells of the cochlea. In this study, we report the effects of quercetin on rat α9α10 nicotinic acetylcholine receptor-mediated ion currents using the two-electrode voltage-clamp technique. Treatment with acetylcholine evoked inward currents (IACh) in oocytes heterologously expressing the α9α10 nicotinic acetylcholine receptor. Quercetin blocked IACh in concentration-dependent and reversible manners, and the blocking effect on IACh was stronger with pre-application than co-application of quercetin. The half maximal inhibitory concentration (IC50) of quercetin was 45.4 ± 10.1 μM. Quercetin-mediated IACh inhibition was not affected by acetylcholine concentration and was independent of membrane-holding potential. Although the inhibitory effect of quercetin was significantly attenuated in the absence of extracellular Ca2+, the action of quercetin was independent of extracellular Ca2+ concentration, indicating that the presence of extracellular Ca2+ might be needed for quercetin-related effects and might play an important role in quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor. These results indicate that quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor could provide a molecular basis for quercetin actions at the cellular level. 相似文献
150.
Liang W Luo Z Ge S Li M Du J Yang M Yan M Ye Z Luo Z 《European journal of pharmacology》2011,(1):317-324
Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5 mg/kg, 30 mg/kg and 50 mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5 mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50 mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50 mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50 mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia. 相似文献