全文获取类型
收费全文 | 12150篇 |
免费 | 649篇 |
国内免费 | 93篇 |
专业分类
耳鼻咽喉 | 122篇 |
儿科学 | 264篇 |
妇产科学 | 209篇 |
基础医学 | 1549篇 |
口腔科学 | 293篇 |
临床医学 | 1179篇 |
内科学 | 3143篇 |
皮肤病学 | 133篇 |
神经病学 | 1364篇 |
特种医学 | 568篇 |
外科学 | 1831篇 |
综合类 | 17篇 |
预防医学 | 341篇 |
眼科学 | 128篇 |
药学 | 742篇 |
中国医学 | 15篇 |
肿瘤学 | 994篇 |
出版年
2023年 | 66篇 |
2022年 | 175篇 |
2021年 | 266篇 |
2020年 | 157篇 |
2019年 | 212篇 |
2018年 | 297篇 |
2017年 | 241篇 |
2016年 | 297篇 |
2015年 | 274篇 |
2014年 | 399篇 |
2013年 | 565篇 |
2012年 | 885篇 |
2011年 | 836篇 |
2010年 | 460篇 |
2009年 | 432篇 |
2008年 | 753篇 |
2007年 | 751篇 |
2006年 | 799篇 |
2005年 | 772篇 |
2004年 | 791篇 |
2003年 | 678篇 |
2002年 | 595篇 |
2001年 | 180篇 |
2000年 | 148篇 |
1999年 | 143篇 |
1998年 | 140篇 |
1997年 | 100篇 |
1996年 | 109篇 |
1995年 | 95篇 |
1994年 | 77篇 |
1993年 | 94篇 |
1992年 | 104篇 |
1991年 | 107篇 |
1990年 | 91篇 |
1989年 | 100篇 |
1988年 | 77篇 |
1987年 | 58篇 |
1986年 | 61篇 |
1985年 | 51篇 |
1984年 | 60篇 |
1983年 | 44篇 |
1982年 | 41篇 |
1981年 | 38篇 |
1980年 | 33篇 |
1979年 | 25篇 |
1978年 | 24篇 |
1977年 | 16篇 |
1975年 | 16篇 |
1974年 | 18篇 |
1973年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
82.
Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line 下载免费PDF全文
Santoni G Lucciarini R Amantini C Jacobelli J Spreghini E Ballarini P Piccoli M Gismondi A 《Infection and immunity》2002,70(7):3804-3815
The signaling pathways triggered by adherence of Candida albicans to the host cells or extracellular matrix are poorly understood. We provide here evidence in C. albicans yeasts of a p105 focal adhesion kinase (Fak)-like protein (that we termed CaFak), antigenically related to the vertebrate p125Fak, and its involvement in integrin-like-mediated fungus adhesion to vitronectin (VN) and EA.hy 926 human endothelial cell line. Biochemical analysis with different anti-chicken Fak antibodies identified CaFak as a 105-kDa protein and immunofluorescence and cytofluorimetric analysis on permeabilized cells specifically stain C. albicans yeasts; moreover, confocal microscopy evidences CaFak as a cytosolic protein that colocalizes on the membrane with the integrin-like VN receptors upon yeast adhesion to VN. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A strongly inhibited C. albicans yeast adhesion to VN and EA.hy 926 endothelial cells. Moreover, engagement of alpha v beta 3 and alpha v beta 5 integrin-like on C. albicans either by specific monoclonal antibodies or upon adhesion to VN or EA.hy 926 endothelial cells stimulates CaFak tyrosine phosphorylation that is blocked by PTK inhibitor. A role for CaFak in C. albicans yeast adhesion was also supported by the failure of VN to stimulate its tyrosine phosphorylation in a C. albicans mutant showing normal levels of CaFak and VNR-like integrins but displaying reduced adhesiveness to VN and EA.hy 926 endothelial cells. Our results suggest that C. albicans Fak-like protein is involved in the control of yeast cell adhesion to VN and endothelial cells. 相似文献
83.
Role of Apoptosis in Autoimmunity 总被引:2,自引:0,他引:2
Autoimmune diseases are characterized by the activity of autoreactive lymphocytes that produce antibodies targeting self tissue or organ for destruction. Although the pathogenesis of these diseases is poorly understood, during the past two decades basic research has indicated apoptosis as the pivotal molecular mechanism leading to autoimmunity. Recently cytokines have been invoked in the regulation of the apoptosis-related factors and death receptors in autoimmune target destruction. These research advances have contributed to the identification of mechanisms controlling autoimmunity for defining novel therapeutic strategies. 相似文献
84.
Efficacy and safety of sublingual immunotherapy. 总被引:7,自引:0,他引:7
Giovanni Passalacqua Laura Guerra Mercedes Pasquali Carlo Lombardi Giorgio Walter Canonica 《Annals of allergy, asthma & immunology》2004,93(1):3-12; quiz 12-3, 103
OBJECTIVE: To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. DATA SOURCES: Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma, and rhinitis. Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. STUDY SELECTION: Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. RESULTS: SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. CONCLUSION: SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising. 相似文献
85.
86.
Francesca Grassi Aldo Giovannelli Sergio Fucile Elisabetta Mattei Fabrizio Eusebi 《Pflügers Archiv : European journal of physiology》1993,425(1-2):117-125
The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca2+ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca2+ ([Ca2+]i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca2+]i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca2+ channels. The stimulation of the nAChR induced transient whole-cell currents (I
ACh). Little or no current was detected in isotonic extracellular Ca2+, with Cs+ in the patch pipette. Cell pretreatment with muscarine reduced I
ACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/ RD cells, muscarinic stimulation increases [Ca2+]i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides. 相似文献
87.
Soluble Antiapoptotic Molecules and Immune Activation in Chronic Heart Failure and Unstable Angina Pectoris 总被引:7,自引:0,他引:7
Fiorina P Astorri E Albertini R Secchi A Mello A Lanfredini M Craveri A Olivetti G Quaini F 《Journal of clinical immunology》2000,20(2):101-106
Programmed myocyte cell death and activation of the immune system have been shown to occur in patients with congestive heart failure. Besides, unstable angina episodes are likely to be associated with immune activation. Our aim was to evaluate the role of changes in circulating levels of soluble Fas (sFas), suggestive of an enhanced inhibitory response to ongoing apoptosis, and soluble IL2 receptor (sIL2-R), indicative of T-lymphocyte activation, in chronic heart failure and unstable angina pectoris. Thirty patients affected by chronic heart failure (20 idiopathic and 10 ischemic cardiomyopathy) and 13 patients with unstable angina were evaluated. Twenty healthy individuals matched for age and gender were used as controls. A complete biochemical determination of indexes of myocardial damage including cardiac troponin I (cTnI) and creatine kinase (MB/CK) was performed. The results demonstrated that mean levels of sFas and sIL2-R were significantly increased in patients affected by chronic heart failure and unstable angina and were not associated with changes in renal function or with serum levels of cTnI. Highest values of sFas were found in NYHA class IV patients (IV NYHA class = 7.39 ± 0.52 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and more elevated in idiopathic than in ischemic cardiomyopathy (3.64 ± 0.40 vs. 1.82 ± 0.37 ng/ml; P < 0.01). Moreover, in chronic heart failure patients sFas and ejection fraction were negatively correlated (P = 0.01), whereas sFas and sIL2-R were positively correlated (P < 0.01). In unstable angina patients too, sFas and sIL2-R appeared to be correlated (P = 0.03); whereas sFas (angina group = 3.18 ± 0.39 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and sIL2-R (angina group = 0.46 ± 0.11 vs. controls = 0.00 UI/ml; P < 0.01) were higher in angina group than in controls. In most of the cases, the increase of sFas was associated with comparable changes in sIL2-R serum levels, indicating that the activation of Fas system is strictly associated with autoimmune–inflammatory reactions. This phenomenon, both in chronic heart failure and in unstable angina, occurs in the absence of biochemical evidences of myocardial damage and seems to parallel the activation of T cell. Soluble Fas could have a role in sustaining inflammatory response and in prolonging the detrimental effects correlated with it in chronic heart failure and angina pectoris. 相似文献
88.
Tardito D Mori S Racagni G Smeraldi E Zanardi R Perez J 《Journal of affective disorders》2003,76(1-3):249-253
BACKGROUND: Abnormal levels of protein kinase A (PKA) were found in patients with bipolar disorder (BD). Since altered levels are generally accompanied by functional modifications, the purpose of this study was to investigate PKA activity in patients with BD. METHODS: PKA activity was assessed in platelets from 20 drug-free bipolar patients and 19 controls. RESULTS: The cAMP-stimulated PKA activity was significantly increased in bipolar patients compared with controls. LIMITATIONS: This study made use of platelets, which may not fully represent changes occurring in specific brain regions. CONCLUSION: This study adds to the growing evidence suggesting that abnormalities of PKA are associated with BD. 相似文献
89.
First evaluations of LPV/RTV (Kaletra) efficacy on HIV-positive patients treated with multiple drugs
Sabbatani S Legnani G Fulgaro C 《Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive》2003,11(1):18-24
At the current epidemic stage, characterized by the rise of antiretroviral drug resistance, it is necessary to administer to HIV-positive patients increasingly effective treatments. This is possible only by means of powerful drugs. In a retrospective study, the authors evaluate 78 patients: 76 pre-treated with multiple drugs and 2 na ves. The 78 patients received LPV/RTV, starting from the fourth 3-month period of 2000 until the first 3-month period of 2002. The average treatment duration was 6.5 ( 5.5) months; the median value 6 months. The efficacy of the LPV/RTV therapeutic regimen was evaluated by a cytofluorimetric count of CD4+ and determination of the HIV viral load. There were 14 drop-out patients (17.9%): 5 because of auto-suspension, 1 due to absence of clinical and virological efficacy, 5 due to side effects (3 hepatopathy, 1 allergy and 1 nausea); three patients were lost on follow-up. There were 64 (82.1%) patients on treatment. Forty patients responded (51.3%) and 13 (16.7%) had uncontrolled viraemia (over than 200 copies/ml). However, the treatment with LPV/RTV was not interrupted for these patients, because in the follow-up they showed an increase in CD4+ values. The authors conclude that the LPV/RTV combination confirms previous findings: it is a drug with a relatively low incidence of side effects, capable of powerful results even in the treatment of patients receiving multiple drugs and thus subjected to the risk of developing antiretroviral drug resistance. 相似文献
90.
Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study 总被引:5,自引:0,他引:5
Plebani A Soresina A Rondelli R Amato GM Azzari C Cardinale F Cazzola G Consolini R De Mattia D Dell'Erba G Duse M Fiorini M Martino S Martire B Masi M Monafo V Moschese V Notarangelo LD Orlandi P Panei P Pession A Pietrogrande MC Pignata C Quinti I Ragno V Rossi P Sciotto A Stabile A;Italian Pediatric Group for XLA-AIEOP 《Clinical immunology (Orlando, Fla.)》2002,104(3):221-230
A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG. 相似文献