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1.
目的探讨细胞角蛋白18-M30片段(CK18-M30)、内毒素在大鼠非酒精性脂肪肝病(NAFLD)转化为非酒精性脂肪性肝炎(NASH)中的促进作用。方法26只大鼠随机分为3组,对照组(NC组):普通饮食;NAFLD组:高脂饮食喂养8周;NASH组:高脂饮食喂养12周。生化仪测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST);光度法测定血清内毒素(ET);ELISA检测血清IL-18、CK18-M30,RT-PCR分析粪便肠道菌群;行苏木精伊红(HE)染色观察肝脏及末端回肠组织病理。结果NAFLD及NASH组相比NC组,小肠黏膜结构由轻到重受到破坏。NAFLD组及NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAFLD活动度积分(NAS)、大肠杆菌属计数显著高于NC组,而双歧杆菌属、乳酸杆菌属计数显著低于NC组,差异有统计学意义(P<0.05);NASH组大鼠血清ET、CK18-M30、肝脂肪变性程度及NAS显著高于NAFLD组,差异有统计学意义(P<0.05);NASH组大鼠血清ALT、AST、IL-18显著高于NC组及NAFLD组,差异有统计学意义(P<0.05),而NAFLD组与NC组间差异无统计学意义(P>0.05)。相关性分析表明ET与大肠杆菌属、IL-18、ALT、AST、NAS均呈正相关(P<0.05),与乳酸杆菌属、双歧杆菌属呈负相关(P<0.05)。CK18-M30与ALT、AST、IL-18、NAS均呈正相关(P<0.05)。结论NAFLD大鼠早期存在肠源性内毒素血症,肠道屏障的损伤可能是内毒素升高的始动因素,肠源性内毒素又可引发肝内炎症反应,导致NASH发生。CK18-M30可作为NASH预测的重要因素。  相似文献   
2.
目的符合透析治疗安全的透析用水是血液透析日常治疗开展的基本保障,根据统计分析内毒素含量的变化规律,探索控制透析用水内毒素含量的管理方式。方法对上海市21家血液净化中心(室)2019年3月至2020年2月期间透析用水的内毒素(endotoxin,ET)含量数据进行汇总与统计分析。结果透析用水内毒素含量在全年的春季与夏季中会存在部分偏高的情况,其中春季送检的样本中,ET含量>0.25 EU/ml比例占当季送检样本的0.57%,ET含量在0.03~0.25EU/ml之间的比例占7.34%;在夏季送检的样本中,ET含量>0.25EU/ml比例占当季送检样本的1.13%,ET含量在0.03~0.25EU/ml之间的比例占3.39%,与秋冬两季水平相比,差异有统计学意义(F=11.392,P值<0.001)。结论严格管控透析用水生产、输送过程的每个环节,规范采样流程、加强反渗机日常维护管理、重视水处理系统及配管的日常消毒等措施可减少血液透析相关的不良反应发生,提高患者透析质量。  相似文献   
3.
The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.  相似文献   
4.
Molecular hydrogen (H2) exerts anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Here we tested the hypothesis that H2 modulates cardiovascular, inflammatory, and thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at different doses (0.1 or 1.5 mg/kg, intravenously, to induce mild or severe SI) in male Wistar rats (250–300 g). LPS or saline was injected immediately before the beginning of 360-minute inhalation of H2 (2% H2, 21% O2, balanced with nitrogen) or room air (21% O2, balanced with nitrogen). Deep body temperature (Tb) was measured by dataloggers pre-implanted in the peritoneal cavity. H2 caused no change in cardiovascular, inflammatory parameters, and Tb of control rats (treated with saline). During mild SI, H2 reduced plasma surges of proinflammatory cytokines (TNF-α and IL-6) while caused an increase in plasma IL-10 (anti-inflammatory cytokine) and prevented fever. During severe SI, H2 potentiated hypothermia, and prevented fever and hypotension, which coincided with reduced plasma nitric oxide (NO) production. Moreover, H2 caused a reduction in surges of proinflammatory cytokines (plasma TNF-α and IL-1β) and prostaglandin E2 [(PGE2), in plasma and hypothalamus], and an increase in plasma IL-10. These data are consistent with the notion that H2 blunts fever in mild SI, and during severe SI potentiates hypothermia, prevents hypotension reducing plasma NO production, and exerts anti-inflammatory effects strong enough to prevent fever by altering febrigenic signaling and ultimately down-modulating hypothalamic PGE2 production.  相似文献   
5.
6.
目的 探讨早期联合测定外周血降钙素原(PCT)、C反应蛋白(CRP)和内毒素对不同病原菌血流感染的脓毒症鉴别诊断的临床价值.方法 回顾性分析2012年1月至2013年12月首都医科大学附属世纪坛医院ICU血培养阳性的脓毒症患者152例,根据血培养结果分革兰阴性杆菌与革兰阳性球菌及真菌血流感染组,分别观察患者入科后第1天的外周血PCT、CRP、内毒素和三者联合后的水平在早期诊断的价值.结果 (1)共收集血流感染病例152例,革兰阴性菌共93例(61.18%),以肺炎克雷伯氏菌、鲍曼不动杆菌、大肠埃希氏菌、洋葱伯克霍尔德菌、铜绿假单胞菌为主;革兰阳性菌43例(28.29%),金黄色葡萄球菌13例(8.55%);真菌16例(10.53%).(2)对三组患者的炎症指标进行比较,革兰阴性菌组内毒素阳性60例(64.52%),革兰阳性菌及真菌组均未检测到内毒素阳性值.革兰阴性菌PCT为7.760 (3.365,28.585) ng/mL,革兰阳性菌为0.705 (0.265,3.225) ng/mL,真菌为1.245 (0.543,1.998) ng/mL,三组间差异具有统计学意义;CRP在革兰阴性菌为(126.01±66.53) mg/L,革兰阳性菌(77.58±54.21) mg/L,真菌(140.14±71.21) mg/L,血流感染真菌组升高更为明显.(3)比较各细菌组的受试者工作特征曲线(ROC曲线)的诊断效应,区分革兰阳性菌组和真菌组的ROC曲线显示,AUCPCT+CRP=0.791,PCT截点为0.92 ng/mL,CRP截点为68.00 mg/L,敏感性为50%,特异性为95.5%;区分革兰阴性菌组和真菌组的ROC曲线显示:AUCPCT+CRP+LPS=0.947,PCT截点为2.16ng/mL,CRP截点为94.10 mg/L时,内毒素阳性为截点,敏感性为82.8%,特异性为100%;区分革兰阴性菌组和革兰阳性菌组的ROC曲线显示AUCPCT+CRP+LPS=90.2%,PCT截点为2.68 ng/mL,CRP截点为106.5 mg/L,内毒素阳性为截点,敏感性为74.2%,特异性为97.7%.结论 重症监护病房的血流感染仍以革兰阴性菌为主,早期联合外周血PCT、CRP、内毒素检测,与单一炎症因子相比,可明显提高对不同病原菌血流感染脓毒症患者早期诊断的敏感性和特异性.  相似文献   
7.
目的 探究脓毒症大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)时高迁移率族蛋白1(high mobility group box 1,HMGB1)参与中性粒细胞(polymorphonuclear neutrophils,PMN)凋亡延迟的相关机制及正丁酸钠(sodium butyrate,SB)的干预效果. 方法 采用随机数字表法将90只健康成年雄性Sprague-Dawley(SD)大鼠随机分为正常对照组(NS组,6只)、内毒素(lipopolysaccharide,LPS)致伤组(LPS组,42只)、HMGB1抑制剂SB干预组(SB组,42只),LPS组、SB组又分为7个时相点(LPS致伤后0.5、1、2、6、12、24、48 h),每个时相点6只动物.LPS组,腹腔注射LPS 5 mg/kg;SB组,腹腔注射LPS 5 mg/kg后0.5 h静脉注射SB,每次剂量500 mg/kg;NS组,腹腔注射生理盐水1 ml.LPS组、SB组于LPS注射后各时点,颈静脉取血检查PMN,取血后左肺灌洗收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),取右肺中叶行HMGB1 mRNA检测;于LPS注射12h时点(NS组大鼠留取颈静脉血、收集BALF、取右肺中叶行HMGB1 mRNA检测),3组大鼠收集左肺BALF后,取右肺下叶检测肺组织湿/干重比(wet/dry weight ratio,W/D),取右肺上叶进行病理组织学检查;于24、48 h时点,LPS组、SB组取右肺下叶检测肺组织W/D、取右肺上叶进行病理组织学检查. 结果 与NS组比较,LPS组肺组织中HMGB1 mRNA表达量明显增高,24 h达最大值,差异有统计学意义(P<0.05);SB组的HMGB1 mRNA表达量减少,差异有统计学意义(P<0.05).LPS组BALF中凋亡早期PMN表达量与NS组类似,但凋亡晚期PMN变化则不同,LPS组外周血中凋亡晚期PMN细胞高于NS组(P<0.05),LPS组BALF中凋亡晚期PMN细胞均低于NS组(P<0.05).LPS 12 h组BALF的PMN百分比明显高于NS组[(49.1±6.8)、(2.7±0.5)],差异有统计学意义(P<0.01).LPS组肺组织光镜下可见肺泡腔水肿,支气管壁中发现PMN浸润,肺泡壁毛细血管扩充血.LPS24 h组肺组织的W/D明显高于NS组[(6.71±0.12)、(4.18±0.26)],差异有统计学意义(P<0.05).SB干预组的HMGB1 mRNA表达量减少,早期凋亡率类似,SB组的BALF晚期凋亡率高于同时点LPS组的BALF,SB外周血组晚期凋亡低于同时点LPS外周血组,差异有统计学意义(P<0.05).SB组BALF的PMN百分比、肺组织病理损伤程度、W/D均低于LPS组,差异有统计学意义(P<0.05). 结论 在大鼠ARDS中,HMGB1 mRNA表达较晚,但持续时间长,SB对HMGB1有潜在的治疗作用,HMGB1可能参与PMN凋亡机制的调节.  相似文献   
8.
Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy.  相似文献   
9.
Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.  相似文献   
10.
Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2 h 45 min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.  相似文献   
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