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Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.  相似文献   
3.

Ethnopharmacological relevance

Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated ( 33 and 37), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats.

Materials and methods

T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35 mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200 mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF.

Results

SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP).

Conclusions

This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF.  相似文献   
4.
目的观察瞬时受体电位阳离子通道-6(transient receptor potential canonical-6,TRPC6)在链脲佐菌素(streptozotocin,STZ)诱导糖尿病(diabetes mellitus,DM)大鼠模型中的表达,并探讨TRPC6在DM肾损害中的作用及意义。方法雄性SD大鼠70只,随机分为正常对照组(normal control group,NCG)15只和实验组(experimental group,EG)55只。实验组采用STZ 70mg/kg单次腹腔注射方式建立DM大鼠模型,按照成模标准去除未成模大鼠。监测各组大鼠的空腹血糖(fasting blood glucose,FBG)、尿蛋白(urine protein,UP)以及肾功能;分别于2、4、8周处死各组大鼠,收取肾脏留做病理及免疫组化;分别对TRPC6与尿蛋白以及肾功能做相关性分析。结果与正常对照组相比,DM组的FPG显著增加(P〈0.05),而DM组各时点间的血糖水平无明显差异;与正常对照组相比,DM组4、8周大鼠的肌酐、尿素氮以及尿蛋白水平显著增加,差异有统计学意义(P〈0.05),而DM组2周大鼠的肌酐、尿素氮以及尿蛋白水平无明显增加(P〉0.05)。与正常对照组相比,DM组的TRPC6表达明显增加,并随着造模时间的延长而继续增加,差异有统计学意义(P〈0.05)。DM组大鼠TRPC6的表达水平分别与肌酐(r=0.745,P〈0.05)、尿素氮水平(r=0.695,P〈0.005)、尿蛋白水平(r=0.713,P〈0.005)呈正相关。结论高血糖可诱导DM大鼠模型肾脏高表达TR-PC6,TRPC6可能参与了糖尿病大鼠模型蛋白尿及肾损害的发生发展。  相似文献   
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目的:探索一种适用于初学者的以STZ法复制1型糖尿病(T1DM)大鼠模型的技术方案?方法:100只雄性Wistar大鼠随机分为模型组(DMM)和对照组(NC)?采用有别于现有文献报道的技术方案即分批次建模?DMM组分3批依次分别一次性腹腔注射60 mg/kg(DMM1)?70 mg/kg(DMM2)?55 mg/kg(DMM3)STZ溶液,NC组注射等量的柠檬酸盐缓冲液?DMM1?DMM2建模未成功者均编为DMM3?将72 h后禁食17 h空腹血糖值(FPG)≥11.1 mmol/L和相应生理指标作为成模的判断依据?结果:DMM1建模前后FPG无差异(P > 0.05),DMM1建模失败;DMM2建模前后FPG具有显著差异(P < 0.05),成模率为75%?DMM3补充剂量后建模成功?结论:分批次进行的STZ法建模方案适宜于初学者使用?  相似文献   
7.
目的观察益气养阴化瘀通络中药对实验性糖尿病大鼠模型的影响。方法除正常对照组外,SD大鼠高脂饲料饲养12周后,腹腔注射STZ 30 mg/kg,成模大鼠随机分为模型组和益气养阴化瘀通络中药治疗组,治疗20周。定期监测大鼠饮水量、饲料消耗量、尿量、体质量和空腹血糖。结果 77.27%大鼠成活成模。与对照组比较,模型组大鼠出现饮水量、饲料消耗量、尿量显著增多,体质量明显减轻,血糖显著升高(P<0.05)。益气养阴化瘀通络中药治疗可显著减轻大鼠"三多一少"表现,与模型组比较,P<0.05,可降低血糖,与模型组比较,P>0.05。随治疗时间延长,效果逐渐明显。结论高脂饲料加小剂量STZ腹腔注射可复制实验性糖尿病大鼠模型,益气养阴化瘀通络中药对其有积极治疗作用。  相似文献   
8.
ABSTRACT

There are conflicting reports regarding the action of streptozotocin (STZ) on blood pressure (BP) in rats. This study investigated the BP, metabolic and hormonal effects of increasing doses of STZ in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), with consideration to methodological aspects. Indirect tail-cuff systolic BP measured in a conscious state was mildly elevated after 2 to 4 weeks and remained so in severely diabetic, emaciated WKY, whereas there were no changes in the SHR. Four and 20 weeks after STZ administration, systolic, mean and diastolic BPs measured in a conscious state with an arterial catheter were unchanged in the diabetic WKY and were decreased in the diabetic SHR. Thus, the changes in BP depended on the method used. Dose-dependent increases in blood glucose were similarly evident under conscious and ether-anesthetized conditions. Triglycerides were increased, and blood insulin and thyroxine levels were decreased in both strains. Between-strain comparisons revealed that the hypoinsulinemic response was similar, but the hyperglycemic and hypertriglyceridemic responses were greater in the SHR. The findings provide a data base for further investigation on STZ diabetes. In addition, the results suggest a different BP and metabolic susceptivity to STZ treatment in the SHR and WKY.  相似文献   
9.
目的研究茶多糖对链脲菌素(STZ)诱导高血糖小鼠血糖血脂的影响,初步探讨茶多糖降血糖的作用机制。方法采用链尿菌素诱导高血糖小鼠模型,给药至第14d、28d测定其空腹血糖;给药至28d,测定血清胆固醇与甘油三酯,取肝脏,测定肝糖原含量。结果茶多糖能显著性降低给药第14d、28d空腹血糖及血清总胆固醇、甘油三酯含量,提高肝糖原含量。结论茶多糖对链脲菌素诱导的高血糖小鼠具有一定的降血糖降血脂的作用,其可能的作用机制是增加肝糖原含量有一定的关系。  相似文献   
10.
Pharmacological activation of AMP activated kinase (AMPK) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes. Despite improved glucose regulation achieved by administration of small molecule activators of AMPK, the potential negative impact of enhanced AMPK activity on insulin secretion by the pancreatic beta cell is an important consideration. In this review, we discuss our current understanding of the role of AMPK in central functions of the pancreatic beta cell, including glucose-stimulated insulin secretion (GSIS), proliferation, and survival. In addition we discuss the controversy surrounding the role of AMPK in insulin secretion, underscoring the merits and caveats of methods used to date.  相似文献   
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