全文获取类型
收费全文 | 1160篇 |
免费 | 86篇 |
国内免费 | 45篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 9篇 |
妇产科学 | 10篇 |
基础医学 | 222篇 |
口腔科学 | 4篇 |
临床医学 | 68篇 |
内科学 | 246篇 |
皮肤病学 | 12篇 |
神经病学 | 164篇 |
特种医学 | 12篇 |
外科学 | 54篇 |
综合类 | 87篇 |
现状与发展 | 1篇 |
预防医学 | 38篇 |
眼科学 | 15篇 |
药学 | 276篇 |
中国医学 | 31篇 |
肿瘤学 | 36篇 |
出版年
2023年 | 7篇 |
2022年 | 13篇 |
2021年 | 32篇 |
2020年 | 22篇 |
2019年 | 39篇 |
2018年 | 31篇 |
2017年 | 33篇 |
2016年 | 54篇 |
2015年 | 44篇 |
2014年 | 77篇 |
2013年 | 86篇 |
2012年 | 99篇 |
2011年 | 102篇 |
2010年 | 65篇 |
2009年 | 74篇 |
2008年 | 100篇 |
2007年 | 71篇 |
2006年 | 35篇 |
2005年 | 39篇 |
2004年 | 37篇 |
2003年 | 33篇 |
2002年 | 25篇 |
2001年 | 21篇 |
2000年 | 13篇 |
1999年 | 15篇 |
1998年 | 11篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 14篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有1291条查询结果,搜索用时 15 毫秒
1.
Abstract Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10?5M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 times 10?7 M) and oxyhaemoglobin (1.6 times 10?5 M), but not affected by atropine (10?7 M), propranolol (10?7 M), phentolamine (10?7 M), indomethacin (10?6 M), chole-cystokinin (CCK, 10?8 M) and vasoactive intestinal polypeptide (VIP, 10?8 M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10?5 M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10?5 M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10?5 M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10?3 M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used. 相似文献
2.
Roland Seifert Rahel Burde Günter Schultz 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(1):101-106
Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O
2
–
) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the Chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E1 (PGE1) with those of various opioids on O
2
–
formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O
2
–
formation in neutrophils with EC50 values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O
2
–
formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [d-Ala2-d-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O
2
–
formation. ATP but not \-endorphin potentiated fMet-Leu-Phe-induced O
2
–
formation. O
2
–
formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE1. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or -endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O
2
–
formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect. In HL-60 cells differentiated with dibutyryl cAMP, fMet-Leu-Phe, PAF and ATP but not -endorphin activated O
2
–
formation. Our results show that O
2
–
formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O
2
–
formation. The precise definition of the experimental conditions and control experiments with established modulators of O
2
–
formation are essential to evaluate the role of opioids in the regulation of this effector system.Send offprint requests to R. Seifert at the above address 相似文献
3.
缺氧性肺动脉高压时一氧化氮合酶、左旋精氨酸及亚硝基左旋精氨酸甲酯的研究 总被引:1,自引:0,他引:1
目的研究一氧化氮(NO)在缺氧性肺动脉高压(HPH)发病中的作用。方法用烟酰胺腺嘌呤二核苷酸磷酸—黄递酶(NicotinamideAdenineDinucleotidePhosphateDiaphorase,NADPHd)和免疫组化ABC方法检测原生型和诱生型一氧化氮合酶(cNOS、iNOS)在正常和缺氧大鼠肺内的表达和分布,同时观察左旋精氨酸(Larg)和亚硝基左旋精氨甲酯(LNAME)对正常和缺氧大鼠肺循环的影响。结果HPH组,NADPHd阳性反应见于大血管内皮、平滑肌、支气管粘膜上皮及小血管内皮和平滑肌中,而后者在正常时未见阳性反应;cNOS在肺血管内皮和支气管粘膜上皮中的表达明显减弱,甚至消失,而正常时不表达iNOS的肺血管内皮和血管、支气管平滑肌在HPH组出现了阳性表达;缺氧时补充Larg和LNAME,与单纯缺氧相比,对右心室肥大和肺血管重建无影响。结论缺氧时cNOS被抑制,可能对HPH的形成具有一定的作用;而iNOS的诱导表达,则可能对HPH的形成具有阻止作用。 相似文献
4.
Ken Dewitte Marc Claeys Emeline Van Craenenbroeck Koen Monsieurs Hein Heidbuchel Vicky Hoymans Tibor Stoop 《Pathophysiology》2019,26(1):53-59
Aims
We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.Methods and results
In 20 healthy male volunteers (mean age 31?±?10 years), flow-mediated dilation (FMD) was measured before and after 20?min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5?min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design.In the control group, IR significantly reduced FMD (5.9?±?2.9% before IR vs. 2.2?±?3.7% after IR; p?<?0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5?±?3.1% before IR vs. 4.0?±?3.4% % after IR; p for interaction?=?0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly.Only changes in SOD levels were significantly related to the degree of RIC induced protection (r²?=?0.34; p?=?0.018).Conclusion
RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines. 相似文献5.
El Benna J Hayem G Dang PM Fay M Chollet-Martin S Elbim C Meyer O Gougerot-Pocidalo MA 《Inflammation》2002,26(6):273-278
Superoxide anion (O2°-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2°-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNF, IL-8 and GM-CSF levels. O2°-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNF and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNF levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNF and IL-8 but not GM-CSF. 相似文献
6.
IFN-γ在沙眼衣原体呼吸道感染中免疫防御机制的探讨 总被引:1,自引:0,他引:1
目的:检测与IFN-γ作用相关的酶吲哚胺2,3二氧化酶(IDO)、诱导性一氧化氮合成酶(iNOS)和NADPH氧化酶(ox)gp91在沙眼衣原体呼吸道感染中的表达及与机体防御的关系,探讨衣原体感染中IFN-γ免疫防御作用的机制.方法:用沙眼衣原体小鼠肺炎株(MoPn)通过鼻腔感染C57BL/6(H-2b)小鼠,用过氧化物酶连接的鼠抗衣原体脂多糖单抗染色HeLa 229细胞,检测衣原体在肺组织的生长;用RT-PCR检测衣原体感染后第7及14天小鼠肺组织IFN-γ、IDO、iNOS和gp91NADPH ox mRNA表达.结果:MoPn呼吸道感染后小鼠肺组织匀浆衣原体活性测定,于感染后第2天,HeLa 229细胞内可见有衣原体包涵体生长,IFU值增高,于感染后第7天IFU达最高水平,以后逐渐下降,至感染后21天基本恢复到基线水平.与未感染的对照组比较,Th1细胞因子IFN-γ于感染后第7天表达显著增高,感染后14天有所降低,但仍维持较高水平;同时衣原体感染可显著诱导与IFN-γ作用相关的三种酶IDO、iNOS和gp91 NADPH ox在小鼠肺组织的表达,感染后第7及14天,IDO,iNOS及gp91 NADPH ox的表达与对照组比较均有显著差异,其中IDO和gp91 NADPH ox于感染后第7天mRNA表达增高显著(P<0.01),14天略有下降(P<0.05).结论:衣原体呼吸道感染诱导Th1细胞因子IFN-γ mRNA高表达,参与宿主对衣原体的清除及机体免疫防御,此作用可能与其相应的酶IDO、iNOS和gp91 NADPH ox表达增高有关. 相似文献
7.
William M. Nauseef 《Immunological reviews》2007,219(1):88-102
Summary: Neutrophils constitute the dominant cell in the circulation that mediates the earliest innate immune human responses to infection. The morbidity and mortality from infection rise dramatically in patients with quantitative or qualitative neutrophil defects, providing clinical confirmation of the important role of normal neutrophils for human health. Neutrophil-dependent anti-microbial activity against ingested microbes represents the collaboration of multiple agents, including those prefabricated during granulocyte development in the bone marrow and those generated de novo following neutrophil activation. Furthermore, neutrophils cooperate with extracellular agents as well as other immune cells to optimally kill and degrade invading microbes. This brief review focuses attention on two examples of the integrated nature of neutrophil-mediated anti-microbial action within the phagosome. The importance and complexity of myeloperoxidase-mediated events illustrate a collaboration of anti-microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and plasma-derived group IIA phospholipase A2 exemplifies the collective effects of the neutrophil with an exogenous factor to achieve degradation of ingested staphylococci. 相似文献
8.
目的探讨七氟烷对兔心肌缺血-再灌注心律失常及还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚单位p22phox表达的影响。方法将兔随机分成3组,假手术组、模型组和七氟烷预处理组。制备兔心肌缺血-再灌注模型,硫代巴比妥酸反应产物(TBARS)显色分光光度比色法测定脂质过氧化物水平,免疫印迹法检测NADPH氧化酶亚单位p22phox表达。结果模型组室性心律失常发生率(90%)和持续时间[(158.82±18.86) s]均较假手术组明显增加(0%,0 s,P<0.01,P<0.01);模型组心肌脂质过氧化物水平[(2.12±0.36) μg8226;g-1]显著高于假手术组[(0.89±0.11) μg8226;g-1,P<0.01],且p22phox亚单位表达显著上调。与模型组比较,七氟烷预处理组室性心律失常发生率(70%)和持续时间[(39.65±5.27) s]、心肌脂质过氧化物水平[(1.35±0.20) μg8226;g-1]及p22phox表达均显著下调。结论七氟烷可抑制兔心肌缺血 再灌注诱导的心律失常,其机制可能与下调p22phox表达进而抑制组织脂质过氧化物水平有关。 相似文献
9.
目的研究NADPH氧化酶在青年和老年大鼠角膜和晶状体上皮细胞中的表达。方法实验分为青年组(3月龄)和老年组(16月龄),比色法测定血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,HE染色观察角膜和晶状体上皮细胞病理形态学变化,免疫组化检测角膜和晶状体上皮细PKCα、P47phox和NOX2的表达。结果与青年组大鼠比较,老年组大鼠血清SOD活性明显降低,MDA含量明显增加。病理结果显示,老年组角膜和晶状体上皮细胞核固缩、核深染细胞增多。免疫组化结果表明,老年组大鼠角膜和晶状体上皮细胞PKCα、P47phox和NOX2的表达明显增加。结论老年大鼠角膜和晶状体上皮细胞NADPH氧化酶表达明显增加,NADPH氧化酶介导的活性氧可能与老龄大鼠角膜和晶状体退行性变有关。 相似文献
10.
Yu-si CHENG De-zai DAI Yin DAI 《中国药理学报》2009,(8):1099-1106
Aim: Spatial dispersion of bioactive substances in the myocardium could serve as pathological basis for arrhythmogenesis and cardiac impairment by β-adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein kinase Cε (PKCε), early response gene (ERG), and matrix metalloproteinase 9 (MMP-9) across the heart by isoproterenol (ISO) medication might be mediated by the endothelin (ET) - ROS pathway. We aimed to verify if ISO induced spatially heterogeneous distribution of pPKCε, NAPDH oxidase, MMP-9 and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS inhibitor aminoguanidine. Methods:Rats were treated with ISO (1 mg/kg sc) for 10 days, and drug interventions (mg/kg) either CPU0213 (30 sc) or aminoguanidine (100 ip) were administered on days 8-10. Expression of NADPH oxidase, MMP-9, ERG, and PKCε in the left and right ventricle (LV, RV) and septum (S) were measured separately. Results: Ventricular hypertrophy was found in the LV, S, and RV, in association with dispersed QTc and oxidative stress in ISO-treated rats. mRNA and protein expression of MMP-9, PKCε, NADPH oxidase and ERG in the LV, S, and RV were obviously dispersed, with augmented expression mainly in the LV and S. Dispersed parameters were re-harmonized by either CPU0213, or aminoguanidine. Conclusion: We found at the first time that ISO-induced dispersed distribution of pPKCε, NADPH oxidase, MMP-9, and ERG in the LV, S, and RV of the heart, which were suppressed by either CPU0213 or aminoguanidine. It indicates that the ET-ROS pathway plays a role in the dispersed distribution of bioactive substances following sustained β-receptor stimulation. 相似文献