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Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium 总被引:12,自引:0,他引:12
van Hinsbergh VW; Bertina RM; van Wijngaarden A; van Tilburg NH; Emeis JJ; Haverkate F 《Blood》1985,65(2):444-451
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. 相似文献
4.
KH Neppelenbroek RS Seó VM Urban S Silva LN Dovigo JH Jorge NH Campanha 《Oral diseases》2014,20(4):329-344
In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. 相似文献
5.
The JB6 mouse epidermal cell system has been used extensively as an in
vitro transformation model for the study of tumor promotion. The standard
JB6 cell assay for promotion of transformation is carried out in soft agar
or other anchorage independent conditions. The present study was directed
to the development of an in vivo model to distinguish the promotion
resistant (P-) and promotion sensitive (P+) progression phenotypes. Results
indicate that the grafting assay distinguishes P- and P+ cells in vivo with
P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant
negative mutant jun TAM67 blocks both anchorage independent transformation
response and graft bed tumor formation by P+ cells, suggesting that the
requirement for AP-1 activation in transformation now applies in vivo.
Expression of mutated p53 produced a gain of P+ phenotype in P- cells in
vitro, but not in vivo. Histochemical and Northern blot analysis for
expression of various keratinocyte markers revealed no evidence for
expression, suggesting a loss of keratinocyte markers following
establishment in culture. In summary, the skin-grafting assay described in
this study appears to be a valid in vivo assay for distinguishing the
preneoplastic progression phenotypes represented by JB6 P- and P+ cells.
相似文献
6.
目的:了解北京市崇文区中老年人原发性骨质疏松症患病情况及其影响因素。方法:①调查对象:选择1998-06/09居住在北京市崇文区具有正式户口的常住男女人群,按照分层多阶段整群抽样方法抽取年龄在40~85岁中老年人为调查对象。②实验方法和评估指标:骨密度测量采用双能X线骨密度测定仪测量308名中老年人腰椎(L2~L4)前后位及股骨上端的骨股颈、三角区(Ward's)和大粗隆的骨密度;问卷调查分为一般情况、月经和生育史、药物应用史、饮食习惯和体格检查情况。结果:308名中老年人接受调查,其中男140名,女168名。年龄40~85岁,平均(60.80±10.12)岁。①各年龄段不同性别中老年人腰椎和股骨上端骨密度测量结果:大粗隆、骨股颈和三角区骨密度无论男女均随着年龄的增长有下降趋势。②各年龄段不同性别中老年人原发性骨质疏松症患病率情况:腰椎、大粗隆和三角区部位的患病率女性高于男性,股骨颈部位的患病率男性高于女性。男性以股骨颈原发性骨质疏松症检出率最高,女性以三角区检出率最高。原发性骨质疏松症患病率随着年龄的增加有增高的趋势。③Ward's三角区骨密度单因素分析:年龄、绝经后年限、生育次数与Ward's三角区骨密度呈负相关(P<0.05);居住环境采光条件、每周蛋类摄入量、身高和体质量与Ward's三角区骨密度呈正相关(P<0.05)。男性和女性、服用钙剂组和未服用钙剂组、服用避孕药物组和未服用避孕药物组、受背痛困扰组和未受背痛困扰之间差异有显著性(P<0.05)。④Ward's三角区骨密度多因素分析:年龄、体质量、绝经年限(女性)是引起骨密度降低的3个重要因素。结论:对于男性人群腰椎骨密度正常,但有明显骨质增生者应参考股骨上端骨密度方能作出正确评价。绝经后高龄妇女、低体质量的人群是原发性骨质疏松的高危人群。 相似文献
7.
国内六大行政区域六城市中老年人群膝关节骨性关节炎患病危险因素比较 总被引:8,自引:3,他引:8
目的:了解中国不同地区间中老年人群膝关节骨性关节炎患病危险因素。方法:调查时间为2005—07/08。①从中国六大行政区(西北,华北,华东。中南,东北,西南)选出六城市(西安,石家庄,上海。广州,哈尔滨市,成都),用分层多阶段整群抽样方法,抽取6218名40岁及以上具有正式户口常住男女人群进行膝关节骨性关节炎的流行病学问卷调查(包括一般情况、现病史、既往史、体格检查、X射线片检查情况和疾病诊断6个方面,共计94个问题141个变量指标),并对其中4808名有症状者进行X射线平片膝正侧位投照。②膝关节骨性关节炎诊断标准为临床症状阳性加X射线Kellgren & Lawrence分级二级及以上者。③计算患病率,并采用Epilnf06.0和SPSS 10.0软件对其中83个变量进行多因素非条件Logistfc回归分析,表示疾病与暴露因素之间联系强度的指标用比值比(OR),若OR〉1,说明疾病发生危险性增加,与暴露因素呈正关联;若OR〈1,说明疾病发生危险性减少,与暴露因素呈负关联。
结果:①六城市膝关节骨性关节炎总患病率为15.6%,其中西安7.7%,石家庄11.2%,上海9.8%。广州30.5%,哈尔滨16.9%,成都17.5%,各城市患病率比较差异显著(P〈0.01)。②Logistic回归分析膝关节骨性关节炎在大部分城市有共同的危险因素如年龄大(OR=1.032—1.181),使用蹲坑排便年限长(OR=1.021-1.077),体质量高(OR=1.048—1.073),和开始饮酒年龄大(OR=1.008~1.028);而从事专职体育运动(OR=1.651,西安),骨质疏松病史(OR=3.311,石家庄),吸烟(OR=2.654,石家庄),类风湿关节炎病史(OR=4.964,上海),文化程度高(OR=2.593,上海),女性(OR=2.510,广州),姐妹骨关节炎史(OR=13.251,哈尔滨),母亲骨关节炎史(OR=5.683,成都)等危险因素分别在不同地区出现.
结论:年龄大、使用蹲坑排便年限长、体质量高和开始饮酒年龄大是中国六地区膝关节骨性关节炎患病的共同危险因素,同时,不同地区主要危险因素又有一定差异。 相似文献
8.
Ming-Tatt L Khalivulla SI Akhtar MN Mohamad AS Perimal EK Khalid MH Akira A Lajis N Israf DA Sulaiman MR 《Basic & clinical pharmacology & toxicology》2012,110(3):275-282
Abstract: This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6‐bis‐(4‐hydroxy‐3‐methoxybenzylidene)cyclohexanone (BHMC), using chemical‐ and thermal‐induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose‐related inhibition in the acetic acid‐induced abdominal constriction test in mice with an ID50 of 0.15 (0.13–0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin‐induced paw licking test with an ID50 of 0.35 (0.27–0.46) mg/kg and 0.07 (0.06–0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot‐plate test. Moreover, the antinociceptive effect of the BHMC in the formalin‐induced paw licking test and the hot‐plate test was antagonized by pre‐treatment with the non‐selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID50 of 0.66 (0.41–1.07) mg/kg and 0.42 (0.38–0.51) mg/kg, respectively. Finally, it was also shown that BHMC‐induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators. 相似文献
9.
Khalid MH Akhtar MN Mohamad AS Perimal EK Akira A Israf DA Lajis N Sulaiman MR 《Journal of ethnopharmacology》2011,137(1):345-351
Ethnopharmacological relevance
Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as “lempoyang”, commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.Aim
The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.Materials and methods
Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.Results
It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID50 values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6 μg/paw) with calculated mean ID50 of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100 mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20 mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10 mg/kg, i.p.), an ATP-sensitive K+ channel antagonist significantly reversed antinociceptive activity induced by EOZZ.Conclusion
Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K+ channel pathway. 相似文献10.
Lisanne M Verweij Karin I Proper Andre NH Weel Carel TJ Hulshof Willem van Mechelen 《BMC public health》2009,9(1):461-17