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21.
Influence of Nicotine on Myocardial Stiffness and Fibrosis During Chronic Ethanol Use 总被引:4,自引:0,他引:4
G. Rajiyah R. Agarwal G. Avendano M. Lyons B. Soni T. J. Regan 《Alcoholism, clinical and experimental research》1996,20(6):985-989
Cardiomyopathy related to ethanol abuse is often accompanied by cigarette use. To examine if the major cardioactive component may intensify the abnormal function and composition induced by chronic ethanol, nicotine was administered orally, 2.5 mg bid, to a canine model receiving 36% of calories as ethanol for 6 months (group III). These animals were compared with group II receiving ethanol alone, group IV on nicotine alone, and controls (group I). In the intact, ventilated, anesthetized dog, left ventricular pressures and volumes were measured before and after dextran infusion and related to left ventricular collagen alterations. Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chamber stiffness (KPV) were significantly higher in the basal state and during dextran infusion in the three experimental groups, compared with group I. The increment was largest in the ethanol-nicotine group. Analysis of left ventricular myocardium revealed a rise of collagen concentrations in all three experimental groups, with an interstitial distribution on histochemical examination. Moreover, determination of advanced glycosylation endproducts, as a measure of alterations in collagen cross-links, revealed higher concentrations versus controls. The greater increase of diastolic stiffness in the nicotine-ethanol group occurred despite a similar concentration of fluorescent products as group II. Because the former had a larger increase of collagen concentration, total cross-linked collagen content was presumably greater after the combined use of nicotine-ethanol. Thus, nicotine in relatively high dose when combined with ethanol, elicited a modest further increase in the left ventricular chamber stiffness and collagen concentration. 相似文献
22.
Prostaglandin D2 synthase (PGDS) is a glycoprotein that is exclusively brain derived and is one of the most abundant proteins in the cerebrospinal fluid (CSF). Due to its high CSF specificity, it can be used as a tool for the diagnosis of central nervous system (CNS) disorders. However, several studies have yielded contradictory CSF PGDS concentrations in various CNS neurodegenerative disorders. Sheep CSF samples from different ages were used in this study and 2-dimensional electrophoresis (2-DE) was applied in PGDS identification and concentration calculation. SYPRO Ruby Protein Gel Stain was the staining method used to stain the 2-DE gel protein spots. Pro-Q Emerald 488 Staining for Glycoproteins was used for the staining of glycoproteins. A total of nine PGDS isoforms were identified and CSF total PGDS concentration was calculated to increase linearly by 44% from young (0.9323 ± 0.0637 mg dL−1) to old (1.3669 ± 0.0558 mg dL−1). However, the proportion of CSF total PGDS as a percentage of CSF total protein was discovered to decrease exponentially with age. This was due to the influence of larger age-related increase in CSF albumin concentration (>200% from young to old) as albumin is the most abundant protein in the CSF (>60% of total CSF proteins). Active deglycosylation was not observed in PGDS isoforms during healthy ageing. Some PGDS isoforms were observed to have age-related increase in glycation. These findings suggest that CSF PGDS concentration is increased during healthy ageing and must be taken into consideration when using PGDS as a potential biomarker in diagnosing CNS neurodegenerative disorders. Whether age-related increase in the glycation of some CSF PGDS isoforms will result in detrimental effects on the PGDS protein function needs further investigations. 相似文献
23.
24.
葡萄籽原花青素对糖基化终产物损伤内皮细胞的保护作用 总被引:1,自引:0,他引:1
目的:研究不同浓度葡萄籽原花青素(GSPC)对糖基化终产物(AGE)作用下人脐静脉内皮细胞的保护作用及其机制。 方法:体外培养人脐静脉内皮细胞(HUVEC),糖孵育法制备糖基化终产物修饰牛血清白蛋白(AGE-BSA)。实验分为6组,即空白对照组、实验对照组(BSA组)、损伤组(AGE组)、损伤加入GSPC低、中、高浓度组。将200mg/L AGE作用于不同浓度GSPC培养4h的内皮细胞,继续培养24?h,以细胞生存活力、血管性假血友病因子(vWF)、一氧化氮(NO)为检测指标。结果:200mg/L AGE抑制HUVEC生存活力,细胞增殖活力下降为正常组的90.53%,GSPC预孵育组细胞生存活力逐渐增加,分别为正常组的0.95、1.12、1.23倍;AGE组vWF生成量较正常对照组明显增加(P<0.01),NO含量较正常对照组明显降低(P<0.01)。GSPC预孵育组可显著降低增高的vWF水平,NO生成量显著高于AGE组(P<0.01), 100mg/L GSPC预处理组NO水平恢复至正常水平。结论:AGE会损伤内皮细胞,抑制内皮细胞的生存活力,减少NO的生成。GSPC可抑制AGE对内皮细胞的损伤作用,且可抑制AGE减少NO生成的作用,并呈浓度依赖性,提示GSPC保护内皮细胞免受AGE损伤的机制可能与增加内皮细胞NO生成量有关。 相似文献
25.
目的 探讨吡格列酮对2型糖尿病肾病患者血清糖基化终产物-肽(AGE-肽)和单核细胞趋化蛋白-1(MCP-1)水平的影响。方法 2型糖尿病伴微量白蛋白尿患者60例,分别接受格列吡嗪控释片(瑞易宁)和吡格列酮治疗6个月。流动注射分析法检测血清AGE-肽,EUSA法检测血清MCP-1。结果 两组患者治疗后血清AGE-肽均较治疗前下降,吡格列酮组明显低于瑞易宁组;吡格列酮组治疗后血清MCP-1较治疗前明显下降,且明显低于瑞易宁组;吡格列酮组治疗后尿白蛋白/肌酐下降值与血清AGE-肽和MCP-1下降值呈明显正相关。结论 吡格列酮降低糖尿病。肾病患者血清AGE-肽和MCP-1水平,可能通过抗炎抗糖基化机制发挥肾保护效应。 相似文献
26.
目的:探讨糖尿病伴贫血患者在测定糖基化血红蛋白时,血红蛋白含量对糖基化血红蛋白测定的影响。方法:回顾性分析126例糖尿病伴贫血患者与132例糖尿病不伴贫血患者,糖基化血红蛋白测量的差异,用果糖胺与2周空腹血糖平均值做平行对照。结果:在相似果糖胺与空腹血糖平均值时,糖尿病伴有贫血的患者糖基化血红蛋白显著低于糖尿病不伴有贫血的患者(P<0.001)。结论:糖尿病伴贫血时血红蛋白浓度对糖基化血红蛋白测定有一定影响,临床对此结果应加以综合处理后进行评价。 相似文献
27.
Summary Enamelins were prepared from the soft enamel of bovine fetuses. They were purified on synthetic hydroxyapatite and separated
in two fractions by affinity chromatography on a ConA-ultrogel column. The two fractions were different with respect to their
electrophoretic behavior, stainability, amino acid composition, phosphorylation, and glycosylation. The ConA-binding fraction,
consisting of three molecular species with apparent molecular weights of 33, 37, and 45 kD, contained organic phosphorus and
high levels of sugars. The Gal/Man ratio suggested a biantennary structure. The ConA-unbound fraction contained two major
molecular species with molecular weights of 70 and 56 kD, and represented 70% of the total enamelin preparation. The amino
acid composition of this fraction showed a higher level of alanine and a lower level of proline when compared with that of
total enamelins. Its sugar composition was unusual, being principally constituted of N-acetyl galactosamine and N-acetyl glucosamine. 相似文献
28.
Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein 总被引:5,自引:0,他引:5
The etiological agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies. To begin to understand its biochemical and immunological properties, we expressed both full-length and ectodomain of the protein in various primate cells. Our results show that the protein has an electrophoretic mobility of about 160-170 kDa. The protein is glycosylated with high mannose and/or hybrid oligosaccharides, which account for approximately 30 kDa of the apparent protein mass. The detection of S-protein by immunoassays was difficult using human convalescent sera, suggesting that the protein may not elicit strong humoral immune response in virus-infected patients. We were able to pseudotype murine leukemia virus particles with S-protein and produce SARS pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner and the infection could be specifically inhibited by convalescent sera. Consistent with low levels of antibodies against S-protein, neutralizing activity was weak with 50% neutralization titers ranging between 1:15 to 1:25. To facilitate quantifying pseudovirus-infected cells, which are stained blue with X-Gal, we devised an automated procedure using an ELISPOT analyzer. The high-throughput capacity of this procedure and the safety of using SARS pseudoviruses should make possible large-scale analyses of neutralizing antibody responses against SARS-CoV. 相似文献
29.
单核细胞RAGE表达上调:慢性肾功能衰竭微炎症的机制 总被引:10,自引:0,他引:10
目的探讨慢性肾功能衰竭(CRF)时细胞表面晚期糖基化终产物(AGE)受体(RAGE)的表达及其在单核细胞介导的炎症反应中的作用。方法96例非糖尿病CRF患者的断面队列研究。用密度梯度离心加免疫磁珠法分离外周血单核细胞(PMC),用特异性抗RAGE抗体染色、流式细胞仪检测PMC表面RAGE表达,Scatchard印迹法分析PMC结合AGE的位点数和亲和力,用ELISA法测定循环新蝶呤、TNF-α、C反应蛋白(CRP)和AGE水平。结果CRF患者PMC表面RAGE表达明显上调并随肾功能恶化而增加(r^2=0.73),RAGE上调程度与血浆AGE水平呈正相关(r=0.71);CRF患者PMC与AGE的结合位点数和亲和力明显高于正常人,在相同剂量AGE刺激下,CRF患者PMC生成的TNF-α明显多于正常PMC,且AGE诱导的TNF-α分泌可被抗RAGE抗体所抑制;患者PMC表面RAGE表达水平与循环TNF-α水平呈正相关(r=0.61),与单核细胞活化标志物——新蝶呤(r=0.65)和急性时相反应蛋白——CRP(r=0.44)呈正相关。结论CRF患者RAGE表达增加,RAGE上调可能通过促发炎症正反馈环导致单核细胞持续活化,从而参与CRF由单核细胞介导的全身微炎症反应。 相似文献
30.
体外孵育的非酶糖基化终产物诱导正常大鼠类糖尿病性视网膜血管病变研究 总被引:6,自引:1,他引:5
目的 探讨外源性非酶糖基化终产物 (advancednon enzymaticglycationendproducts ,AGE)在血管壁的沉积与糖尿病性视网膜血管病变之间的关系。方法 将 16只健康两月龄SD大鼠 ,随机分为 4组 ,每组 4只鼠。正常对照组不做任何处理 ;糖尿病对照组应用AGE制作糖尿病模型 ;血清白蛋白 (ratserumalbumin ,RSA)组每日自鼠尾静脉注射RSA(4 0mg kg体重 ) ,连续注射 2周 ;AGE RSA组注射AGE RSA ,注射方法、剂量与RSA组相同。 2周后观察各组鼠视网膜毛细血管周细胞密度变化。结果 注射RSA组鼠视网膜毛细血管周细胞数平均为 (5 80± 0 4 8)个 每油镜视野 ,注射AGE组为(4 31± 0 34)个 每油镜视野 ,显示实验组毛细血管周细胞密度低于对照组 ,差异有显著意义 (F =7 16 4 ,P <0 0 1)。结论 外源性AGE注入正常大鼠会引起类糖尿病性视网膜血管病变 ,AGE可能是糖尿病性视网膜血管病变的独立致病因素之一。 相似文献