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991.
Lemos PA de Feyter PJ Serruys PW Saia F Arampatzis CA Disco C Mercado N Mainar V Morís C van den Bos AA Berghoefer G 《International journal of cardiology》2005,98(3):479-486
BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment. 相似文献
992.
LeVan TD Von Essen S Romberger DJ Lambert GP Martinez FD Vasquez MM Merchant JA 《American journal of respiratory and critical care medicine》2005,171(7):773-779
RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers. 相似文献
993.
The prevalence and natural history of spontaneous bacterial peritonitis in asymptomatic patients with ascites secondary to cirrhosis is unknown. From a prospectively recorded database, we reviewed the clinical and laboratory features of all outpatients with cirrhotic ascites undergoing paracentesis between July 1994 and December 2000. The prevalence of spontaneous bacterial peritonitis in the population of 427 cirrhotic outpatients as defined by neutrocytic ascites (absolute neutrophil count >or=250 cells/mm(3)) was 3.5%. Of the 15 patients with neutrocytic ascites, 6 were culture positive (1.4%) and 9 culture negative (2.1%). Eight other patients (1.9%) had bacterascites. The organisms cultured from ascitic fluid in these asymptomatic patients with culture positive neutrocytic ascites and bacterascites were predominantly gram positive. No patient developed hepatorenal syndrome, and 1-year survival of 67% was better than historical data from hospitalized patients with spontaneous bacterial peritonitis. Moreover, patients who did not receive antibiotics for neutrocytic ascites fared no worse than patients who did receive antibiotics. In conclusion, spontaneous bacterial peritonitis in outpatients with cirrhotic ascites is less frequent, occurs in patients with less advanced liver disease, and may have a better outcome than its counterpart in hospitalized patients. In addition, the organisms cultured from ascitic fluid in outpatients are predominantly gram positive. A reassessment of diagnostic criteria for spontaneous bacterial peritonitis in outpatients may be required. 相似文献
994.
Pettifor AE Kleinschmidt I Levin J Rees HV MacPhail C Madikizela-Hlongwa L Vermaak K Napier G Stevens W Padian NS 《Tropical medicine & international health : TM & IH》2005,10(10):971-980
OBJECTIVES: To determine whether South African youths living in communities that had either of two youth human immunodeficiency virus (HIV) prevention interventions [(a) loveLife Youth Centre or (b) loveLife National Adolescent Friendly Clinic Initiative] would have a lower prevalence of HIV, sexually transmitted infections (STIs), and high risk sexual behaviours than communities without either of these interventions. METHODS: In 2002 the baseline survey of a quasi-experimental, community-based study was conducted in South Africa. In total 33 communities were included in three study arms (11 communities per study arm). The final sample included 8735 youths aged 15-24 years. All participants took part in a behavioural interview and were tested for HIV, gonorrhoea (Neisseria gonorrhoeae) and Chlamydia (Chlamydia trachomatis). RESULTS: HIV prevalence was 20.0% among females and 7.5% among males (OR 3.93 95% CI 2.51-6.15). There were no significant differences between study arms for HIV, NG or CT prevalence at baseline. In multiple regression analyses, HIV was significantly associated with NG infection (OR 1.96 95% CI 1.24-3.12) but not with CT infection. Youths who reported >1 lifetime partner were also significantly more likely to be infected with HIV (OR 1.98 95% CI 1.55-2.52), as were those who reported ever having engaged in transactional sex (OR 1.86 P = 0.02) or having had genital ulcers in the past 12 months (OR 1.71 P < or = 0.001). CONCLUSIONS: HIV prevention programmes must ensure that gender inequities that place young women at greater risk for HIV infection are urgently addressed and they must continue to emphasize the importance of reducing the number of sexual partners and STI treatment. 相似文献
995.
996.
Wadi Mawad Lasse Løvstakken Solveig Fadnes Thomas Grønli Patrick Segers Luc Mertens Siri Ann Nyrnes 《Ultrasound in medicine & biology》2021,47(6):1514-1527
Using blood speckle tracking (BST) based on high-frame-rate echocardiography (HFRE), we compared right ventricle (RV) flow dynamics in children with atrial septal defects (ASDs) and repaired tetralogy of Fallot (rTOF). Fifty-seven children with rTOF with severe pulmonary insufficiency (PI) (n = 21), large ASDs (n = 11) and healthy controls (CTL, n = 25) were included. Using a flow phantom, we studied the effects of imaging plane and smoothing parameters on 2-D energy loss (EL). RV diastolic EL was similar in ASD and rTOF, but both were greater than in CTL. Locations of high EL were similar in all groups in systole, occurring in the RV outflow tract and around the tricuspid valve leaflets in early diastole. An additional apical early diastolic area of EL was noted in rTOF, corresponding to colliding tricuspid inflow and PI. The flow phantom revealed that EL varied with imaging plane and smoothing settings but that the EL trend was preserved if kept consistent. 相似文献
997.
998.
Patrick J. Cimino Yue Yang Xianwu Li Jake F. Hemingway Makenzie K. Cherne Shawn B. Khademi Yoshinori Fukui Kathleen S. Montine Thomas J. Montine C. Dirk Keene 《Experimental and molecular pathology》2013
Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2 −/−), were hemizygous for DOCK2 (DOCK2 +/−), or that expressed two DOCK2 genes (DOCK2 +/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2 −/− mice compared with APPswe-PS1Δe9/DOCK2 +/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD. 相似文献
999.
Janelle C. Waite Santosh Vardhana Patrick J. Shaw Jung‐Eun Jang Christie‐Ann McCarl Thomas O. Cameron Stefan Feske Michael L. Dustin 《European journal of immunology》2013,43(12):3343-3354
Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca2+]i) elevation. TCR activation triggers increased [Ca2+]i and can arrest T‐cell motility in vitro. However, the requirement for [Ca2+]i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca2+ release‐activated Ca2+ (CRAC) channel pathway required for [Ca2+]i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant‐negative ORAI1 channel subunit (ORAI1‐DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4+ T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1‐DN lacked TCR activation induced [Ca2+]i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen‐specific ORAI1‐DN T cells had a twofold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest. 相似文献
1000.
Elio Schouppe Camille Mommer Kiavash Movahedi Damya Laoui Yannick Morias Conny Gysemans Ariane Luyckx Patrick De Baetselier Jo A. Van Ginderachter 《European journal of immunology》2013,43(11):2930-2942
Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b+CD115+Ly6G?Ly6Chigh MDSCs and granulocytic CD11b+CD115?Ly6G+Ly6Cint polymorphonuclear (PMN)‐MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8+ T‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD8+ T‐cell proliferation, but differ in their dependency on IFN‐γ, STAT‐1, IRF‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL‐2 levels, but only MO‐MDSCs affect IL‐2Rα (CD25) expression and STAT‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN‐γ production by CD8+ T cells on a per cell basis, illustrating that some T‐cell activation characteristics are actually stimulated by MDSCs. Conversely, MO‐MDSCs counteract the activation‐induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8+ T‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL‐mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8+ T‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated. 相似文献