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991.
Cleverton Cesar Spautz MSc Eduardo Schunemann Junior MSc Lucas Roskamp Budel MD Tereza Cristina Santos Cavalcanti PhD Maria Helena Louveira PhD Plinio Gasperin Junior PhD Leonardo Paese Nissen MD Bernardo Passos Sobreiro PhD Maíra Teixeira Dória MSc Cicero Andrade Urban PhD Vinicius Milani Budel PhD 《Journal of surgical oncology》2020,122(2):164-169
992.
Johanna C. Bendell Tamara Sauri Antonio Cubillo Gracián Rafael Alvarez Carlos López-López Pilar García-Alfonso Maen Hussein Maria-Luisa Limon Miron Andrés Cervantes Clara Montagut Cristina Santos Vivas Alberto Bessudo Patricia Plezia Veerle Moons Johannes Andel Jaafar Bennouna Andre van der Westhuizen Leslie Samuel Simona Rossomanno Christophe Boetsch Angelika Lahr Izolda Franjkovic Florian Heil Katharina Lechner Oliver Krieter Herbert Hurwitz for the McCAVE Study Group 《The oncologist》2020,25(3):e451-e459
993.
994.
Palacios R Galindo MJ Arranz JA Lozano F Estrada V Rivero A Morales D Asensi V del Arco A Muñoz A Santos J 《HIV medicine》2007,8(1):17-21
OBJECTIVES: The aim of the study was to analyse the prevalence of cervical lipomatosis (CL) in HIV-infected patients on highly active antiretroviral therapy (HAART) and the factors associated with its development. METHODS: This was a multicentre, observational, 1:1 case-control study. HIV-infected patients with CL (cases) and HIV-infected patients from the same cohort, controlled for age (+/-5 years), sex and body mass index (+/-2.5 kg/m(2)) (controls), were included in the study, and a multiple conditional logistic regression was performed to identify factors related to CL. RESULTS: CL was reported in 80 patients (1.8%) from a cohort of 4214 patients on HAART followed up in 10 Spanish hospitals. CL was associated with time of exposure to stavudine [for each 6-month increase, odds ratio (OR) 5.82, 95% confidence interval (CI) 5.70-5.94, P=0.0073] and lipoatrophy (OR 8.04, 95% CI 2.93-22.02, P=0.00001). CONCLUSIONS: Although lipodystrophy is very frequent among HIV-infected patients on HAART, CL is an uncommon type of fat redistribution in this population, and in our cohort it was related to time of exposure to stavudine and lipoatrophy. 相似文献
995.
Leleu X Xu L Jia X Sacco A Farag M Hunter ZR Moreau AS Ngo HT Hatjiharissi E Ho AW Santos DD Adamia S O'Connor K Ciccarelli B Soumerai J Manning RJ Patterson CJ Roccaro AM Ghobrial IM Treon SP 《Blood》2009,113(3):626-634
Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoma characterized by bone marrow (BM) involvement of IgM secreting lymphoplasmacytic cells. The induction of unfolded protein response (UPR) genes ("physiologic" UPR) enables cells to differentiate into professional secretory cells capable of production of high amounts of endoplasmic reticulum (ER)-processed proteins, such as immunoglobulins. Ultimately, the initially cytoprotective UPR triggers an apoptotic cascade if ER stress is not corrected, called proapoptotic/terminal UPR. We show that WM cells inherently express the physiologic UPR machinery compared with normal BM cells, and that increased ER stress leads to proapoptotic/terminal UPR in WM cells. We therefore examined tunicamycin, ER stress inducer, for potential antitumor effects in WM. Tunicamycin induced significant cytotoxicity, apoptosis and cell-cycle arrest, and inhibited DNA synthesis in WM cell lines and primary BM CD19(+) cells from patients with WM with an inhibitory concentration (IC(50)) of 0.5 microg/mL to 1 microg/mL, but not in healthy donor cells. Importantly, coculture of WM cells in the context of the BM microenvironment did not inhibit tunicamycin-induced cytotoxicity. Finally, we demonstrate that ER stress inducer synergizes with other agents used in the treatment of WM. These preclinical studies provide a framework for further evaluation of ER stress inducing agents as therapeutic agents in WM. 相似文献
996.
Silva Sara Pereira Beserra-Filho José Ivo Araújo Kubota Melina Chiemi Cardoso Gabriela Nascimento Freitas Francisca Rayanne Silva Gonçalves Bianca Santos Martins Vicente-Silva Wilson Silva-Martins Suellen Custódio-Silva Ana Claúdia Soares-Silva Beatriz Maria-Macêdo Amanda Santos José Ronaldo Estadella Debora Ribeiro Alessandra Mussi 《Metabolic brain disease》2021,36(7):1717-1727
Metabolic Brain Disease - Worldwide, the excessive consumption of fat and/or sugar has increased considerably. Palatable high-fat diets (HFDs) lead to metabolic disturbances and obesity,... 相似文献
997.
OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. METHODS: A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. RESULTS: Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. CONCLUSIONS: Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART. 相似文献
998.
Itamar S. Santos Márcio S. Bittencourt Ilka R.S. Oliveira Angelita G. Souza Danilo P. Meireles Tatjana Rundek Murilo Foppa Daniel C. Bezerra Cláudia M.V. Freire Leonard H. Roelke Sayonara Carrilho Isabela M. Benseñor Paulo A. Lotufo 《Atherosclerosis》2014
Objective
Carotid intima–media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture.Methods
The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35–74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors.Results
We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (β = 0.058; P < 0.001). This association remained for low-risk individuals (β = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (β = −0.034 and β = −0.054, respectively; P < 0.001) and low-risk individuals (β = −0.027; P = 0.013 and β = −0.035; P < 0.001, respectively).Conclusion
We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals. 相似文献999.
Ramos-Trujillo E González-Acosta H Flores C García-Nieto V Guillén E Gracia S Vicente C Espinosa L Maseda MA Santos F Camacho JA Claverie-Martín F 《Journal of human genetics》2007,52(3):255-261
Mutations in the voltage-gated chloride/proton antiporter ClC-5 gene, CLCN5, are associated with Dent’s disease, an X-linked renal tubulopathy. Our interest is to identify and characterize disease-causing
CLCN5 mutations, especially those that alter the splicing of the pre-mRNA. We analyzed the CLCN5 gene from nine unrelated Spanish Dent’s disease patients and their relatives by DNA sequencing. Pre-mRNA splicing analysis
was performed by RT-PCR. Seven new mutations were identified, consisting of three missense mutations (C219R, F273L, and W547G),
one splice-site mutation (IVS-2A > G), one deletion (976delG), and two non-sense mutations (Y140X and W314X). We found that
missense mutation W547G also led to increased expression of a new alternative isoform lacking exons 10 and 11 that was expressed
in several human tissues. In addition, we describe another novel CLCN5 splicing variant lacking exon 11 alone, which was expressed only in human skeletal muscle. We conclude that missense mutation
W547G can also alter the expression levels of a CLCN5 mRNA splicing variant. This type of mutation has not been previously described in the CLCN5 gene. Our results support the importance of a routine analysis at the pre-mRNA level of mutations that are commonly assumed
to cause single amino acids alterations. 相似文献
1000.
The Central Executioner of Apoptosis: Multiple Connections between Protease Activation and Mitochondria in Fas/APO-1/CD95- and Ceramide-induced Apoptosis 总被引:30,自引:0,他引:30
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Santos A. Susin Naoufal Zamzami Maria Castedo Eric Daugas Hong-Gang Wang Stephan Geley Florence Fassy John C. Reed Guido Kroemer 《The Journal of experimental medicine》1997,186(1):25-37
According to current understanding, cytoplasmic events including activation of protease cascades and mitochondrial permeability transition (PT) participate in the control of nuclear apoptosis. However, the relationship between protease activation and PT has remained elusive. When apoptosis is induced by cross-linking of the Fas/APO-1/CD95 receptor, activation of interleukin-1β converting enzyme (ICE; caspase 1) or ICE-like enzymes precedes the disruption of the mitochondrial inner transmembrane potential (ΔΨm). In contrast, cytosolic CPP32/ Yama/Apopain/caspase 3 activation, plasma membrane phosphatidyl serine exposure, and nuclear apoptosis only occur in cells in which the ΔΨm is fully disrupted. Transfection with the cowpox protease inhibitor crmA or culture in the presence of the synthetic ICE-specific inhibitor Ac-YVAD.cmk both prevent the ΔΨm collapse and subsequent apoptosis. Cytosols from anti-Fas–treated human lymphoma cells accumulate an activity that induces PT in isolated mitochondria in vitro and that is neutralized by crmA or Ac-YVAD.cmk. Recombinant purified ICE suffices to cause isolated mitochondria to undergo PT-like large amplitude swelling and to disrupt their ΔΨm. In addition, ICE-treated mitochondria release an apoptosis-inducing factor (AIF) that induces apoptotic changes (chromatin condensation and oligonucleosomal DNA fragmentation) in isolated nuclei in vitro. AIF is a protease (or protease activator) that can be inhibited by the broad spectrum apoptosis inhibitor Z-VAD.fmk and that causes the proteolytical activation of CPP32. Although Bcl-2 is a highly efficient inhibitor of mitochondrial alterations (large amplitude swelling + ΔΨm collapse + release of AIF) induced by prooxidants or cytosols from ceramide-treated cells, it has no effect on the ICE-induced mitochondrial PT and AIF release. These data connect a protease activation pathway with the mitochondrial phase of apoptosis regulation. In addition, they provide a plausible explanation of why Bcl-2 fails to interfere with Fas-triggered apoptosis in most cell types, yet prevents ceramide- and prooxidant-induced apoptosis. 相似文献