全文获取类型
收费全文 | 9756篇 |
免费 | 565篇 |
国内免费 | 519篇 |
专业分类
耳鼻咽喉 | 86篇 |
儿科学 | 121篇 |
妇产科学 | 117篇 |
基础医学 | 1570篇 |
口腔科学 | 152篇 |
临床医学 | 560篇 |
内科学 | 1548篇 |
皮肤病学 | 99篇 |
神经病学 | 1021篇 |
特种医学 | 158篇 |
外科学 | 664篇 |
综合类 | 1496篇 |
现状与发展 | 2篇 |
预防医学 | 366篇 |
眼科学 | 108篇 |
药学 | 1633篇 |
中国医学 | 579篇 |
肿瘤学 | 560篇 |
出版年
2024年 | 2篇 |
2023年 | 47篇 |
2022年 | 105篇 |
2021年 | 125篇 |
2020年 | 134篇 |
2019年 | 138篇 |
2018年 | 147篇 |
2017年 | 156篇 |
2016年 | 190篇 |
2015年 | 221篇 |
2014年 | 462篇 |
2013年 | 593篇 |
2012年 | 551篇 |
2011年 | 692篇 |
2010年 | 553篇 |
2009年 | 591篇 |
2008年 | 675篇 |
2007年 | 725篇 |
2006年 | 662篇 |
2005年 | 593篇 |
2004年 | 670篇 |
2003年 | 579篇 |
2002年 | 488篇 |
2001年 | 377篇 |
2000年 | 300篇 |
1999年 | 240篇 |
1998年 | 203篇 |
1997年 | 174篇 |
1996年 | 122篇 |
1995年 | 99篇 |
1994年 | 58篇 |
1993年 | 46篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 5篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 12篇 |
1983年 | 4篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 5篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
1.
Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ12,14PGJ2 a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ12,14PGJ2 production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ2 and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment. 相似文献
2.
Ceramide synthases (CerS) synthesise ceramides of defined acyl chain lengths, which are thought to mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed a significant elevation of CerS2 and its products, C24-ceramides, in CD11b+ cells (monocytes and neutrophils) isolated from blood. This result correlates with the clinical finding that CerS2 mRNA expression and C24-ceramide levels were significantly increased by 2.2- and 1.5-fold, respectively, in white blood cells of MS patients. The increased CerS2 mRNA/C24-ceramide expression in neutrophils/monocytes seems to mediate pro-inflammatory effects, since a specific genetic deletion of CerS2 in blood cells or a total genetic deletion of CerS2 significantly delayed the onset of clinical symptoms, due to a reduced infiltration of immune cells, in particular neutrophils, into the central nervous system. CXCR2 chemokine receptors, expressed on neutrophils, promote the migration of neutrophils into the central nervous system, which is a prerequisite for the recruitment of further immune cells and the inflammatory process that leads to the development of MS. Interestingly, neutrophils isolated from CerS2 null EAE mice, as opposed to WT EAE mice, were characterised by significantly lower CXCR2 receptor mRNA expression resulting in their reduced migratory capacity towards CXCL2. Most importantly, G-CSF-induced CXCR2 expression was significantly reduced in CerS2 null neutrophils and their migratory capacity was significantly impaired. In conclusion, our data strongly indicate that G-CSF-induced CXCR2 expression is regulated in a CerS2-dependent manner and that CerS2 thereby promotes the migration of neutrophils, thus, contributing to inflammation and the development of EAE and MS. 相似文献
3.
Roberto V.P. Ribeiro Mitesh V. Badiwala Danny Ramzy Laura C. Tumiati Vivek Rao 《The Journal of thoracic and cardiovascular surgery》2019,157(2):615-625.e1
Objective
Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.Methods
Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.Results
Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).Conclusions
Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction. 相似文献4.
5.
目的:检测诱导型和内皮型一氧化氮合酶(iNOS 和eNOS)在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达。方法:采用免疫组织化学SABC法检测iNOS和eNOS在30例外阴慢性单纯性苔藓蜡块(LSC)、30例外阴硬化性苔藓蜡块(LS)和10例外阴正常皮肤中的表达,并以人原始造血细胞抗原(CD34)标记微血管内皮细胞,测量各组织的微血管密度(MVD)。结果:iNOS和eNOS在外阴正常皮肤中无表达;在LSC中iNOS和eNOS每视野平均阳性细胞数分别为14.83±3.79和17.86±4.82,高于LS的8.00±3.35和6.43±3.87,差异均有统计学意义(P<0.05);在LSC和正常皮肤中MVD分别为21.58±2.48和20.44±3.66,高于LS(10.34±2.83)。iNOS和eNOS的表达具有明显的正相关性(Kappa=0.811,P<0.05)。结论:iNOS和eNOS可能与LSC炎症过程中的血管扩张有关;在LS皮损真皮中微血管减少,iNOS和eNOS可代偿性地改善LS的血液循环。 相似文献
6.
目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶(NOS)活力的调节。方法用1000ng/ml脂多糖(LPS)刺激小胶质细胞,分别加入100nmol/L A2A受体激动剂CGS21680以及不同浓度的谷氨酸(0,1,0,25,0,5mmol/L)干预,观察NOS活力变化。结果LPS诱导NOS活力增高,激活A2A受体可以产生抑制作用;0,25及0.5mmoL/L谷氨酸和A2A受体激动剂同时存在时,NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。 相似文献
7.
氯胺酮对大鼠丘脑一氧化氮合酶活性和一氧化氮含量的影响 总被引:4,自引:0,他引:4
目的:观察不同剂量的氯胺酮对大鼠丘脑一氧化氮合酶(NOS)和一氧化氮(NO)含量的影响。方法:Sprague Dawley(SD)大鼠32只,雌雄不限,体重200-300g。随机分为四组(n=8):组I为对照组,给予生理盐水10ml/kg腹腔注射;组Ⅱ、组Ⅲ和组Ⅳ分别给予氯胺酮35ml/kg,100ml/kg和200ml/kg。组I和组Ⅱ在用药后5min后断头取材,组Ⅲ和组Ⅳ在大鼠翻正反射消失后立即断头取材。在低温操作箱内生理盐水冰面上取脑,以分光光度法测定NOS活性和NO量,Lawry法测蛋白含量。结果:大鼠腹腔注射氯胺酮35ml/kg后,其丘脑的NOS活性和NO量与对照组相比均无明显变化(P>0.05)而腹腔注射氯胺酮100ml/kg和200ml/kg后,NOS活性明显降低,分别较对照组降低了44.3%和40%(P<0.05)和P<0.01),NO量也明显减少,分别较对照组减少了42.9%和47.1%(P<0.05)或(P<0.01);且这两组的NOS活性和NO量也明显低于氯胺酮35ml/kg组,NOS活性分别降低了47.3%和43.2%(P<0.01),NOS量降低了47.4%和51.3%(P<0.01);此两组之间相比较,丘脑的NOS活性和NO量无统计学意义(P>0.05)。结论:NO在氯胺酮的中枢作用机制中可能发挥重要作用。 相似文献
8.
去势后大鼠海马结构一氧化氮合酶阳性神经元的变化 总被引:8,自引:1,他引:7
目的:观察去势后大鼠海马结构一氧化氮合酶(NOS)阳性神经元的变化。方法:用黄递酶组织化学染色方法观察切除双侧卵巢后雌后SD大鼠海马结构NOS阳性神经元的形态,分布的变化,并进行计算机图像分析。结果:去势后海马结构NOS阳性神经元分布变化有区域差异性;NOS阳性神经元在下托、海马(CA)一区邻近下托的部分、CA三区、CA四区(CA4)和齿状回(DG)数目明显减少,而在CA二区数目明显明显增多,CA4和DG的NOS阳性神经元平均密度降低,胞体的平均周长和平均截面积都明显减少。结论:雌激素可能通过影响海马结构NOS的表达来影响学习和记忆。 相似文献
9.
10.
血管内皮型一氧化氮合酶基因Glu298 Asp多态性与老年脑梗死的相关性研究 总被引:1,自引:0,他引:1
目的 通过病例对照研究 ,了解中国老年人群血管内皮型一氧化氮合酶 (eNOS)基因目的 通过病例对照研究 ,了解中国老年人群血管内皮型一氧化氮合酶 (eNOS)基因Glu2 98Asp多态性的分布 ,分别探讨其与老年脑梗死及血脂以及一氧化氮等脑梗死危险因素的关系。 方法对门诊及住院中确诊的 4 0例老年脑梗死和 16 9例性别、年龄相匹配的老人 ,测量他们的身高、体重及座位血压 ,并测定他们的空腹血脂、空腹血糖 (FBS)及一氧化氮 (NO)等 ,应用聚合酶链反应 (PCR)和限制性片断长度多态性 (RFLP)检测eNOS基因Glu2 98Asp多态性。结果 脑梗死和对照组eNOS基因Glu2 98Asp多态性构成有显著性差异 (χ2 =4 31,P =0 0 38) ,脑梗死组Glu/Asp基因型高于对照组(32 5 %vs 17 8% ) ;脑梗死组 2 98Asp等位基因频率高于对照组 (16 2 5 %vs 8 9% ) ,但是两组等位基因频率的分布比较 ,没有显著性差异 (χ2 =3 81,P =0 0 5 1)。结论 eNOS基因Glu2 98Asp多态性在中国老年人群中存在 ,并且基因... 相似文献