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21.
Leonard Schuele Hayley Cassidy Erley Lizarazo Katrin Strutzberg-Minder Sabine Schuetze Sandra Loebert Claudia Lambrecht Juergen Harlizius Alex W. Friedrich Silke Peter Hubert G. M. Niesters John W. A. Rossen Natacha Couto 《Viruses》2020,12(12)
Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative. 相似文献
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Baeza-Raja B Li P Le Moan N Sachs BD Schachtrup C Davalos D Vagena E Bridges D Kim C Saltiel AR Olefsky JM Akassoglou K 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(15):5838-5843
Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated translocation of GLUT4 from its intracellular compartment to the plasma membrane is regulated by small guanosine triphosphate hydrolases (GTPases) and is essential for the maintenance of normal glucose homeostasis. Here we show that the p75 neurotrophin receptor (p75(NTR)) is a regulator of glucose uptake and insulin resistance. p75(NTR) knockout mice show increased insulin sensitivity on normal chow diet, independent of changes in body weight. Euglycemic-hyperinsulinemic clamp studies demonstrate that deletion of the p75(NTR) gene increases the insulin-stimulated glucose disposal rate and suppression of hepatic glucose production. Genetic depletion or shRNA knockdown of p75(NTR) in adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4 translocation. Conversely, overexpression of p75(NTR) in adipocytes decreases insulin-stimulated glucose transport. In adipocytes, p75(NTR) forms a complex with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5 and Rab31 directly interact with p75(NTR) primarily via helix 4 of the p75(NTR) death domain. Adipocytes from p75(NTR) knockout mice show increased Rab5 and decreased Rab31 activities, and dominant negative Rab5 rescues the increase in glucose uptake seen in p75(NTR) knockout adipocytes. Our results identify p75(NTR) as a unique player in glucose metabolism and suggest that signaling from p75(NTR) to Rab5 family GTPases may represent a unique therapeutic target for insulin resistance and diabetes. 相似文献
24.
Fabre C Koscielny S Mohty M Fegueux N Blaise D Maillard N Tabrizi R Michallet M Socié G Yakoub-Agha I Garban F Uzunov M François S Contentin N Lapusan S Bourhis JH 《Haematologica》2012,97(4):482-490
Background
How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).Design and Methods
This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.Results
Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.Conclusions
We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies. 相似文献25.
Carolina Maso Viegas Anelise Miotti Tonin ?ngela Zanatta Bianca Seminotti Estela Natacha Brandt Busanello Carolina Gon?alves Fernandes Alana Pimentel Moura Guilhian Leipnitz Moacir Wajner 《Metabolic brain disease》2012,27(4):521-530
Ornithine, ammonia and homocitrulline are the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a genetic disorder characterized by neurological regression whose pathogenesis is still not understood. The present work investigated the in vivo effects of intracerebroventricular administration of ornithine and homocitrulline in the presence or absence of hyperammonemia induced by intraperitoneal urease treatment on a large spectrum of oxidative stress parameters in cerebral cortex from young rats in order to better understand the role of these metabolites on brain damage. Ornithine increased thiobarbituric acid-reactive substances (TBA-RS) levels and carbonyl formation and decreased total antioxidant status (TAS) levels. We also observed that the combination of hyperammonemia with ornithine resulted in significant decreases of sulfhydryl levels, reduced glutathione (GSH) concentrations and the activities of catalase (CAT) and glutathione peroxidase (GPx), highlighting a synergistic effect of ornithine and ammonia. Furthermore, homocitrulline caused increases of TBA-RS values and carbonyl formation, as well as decreases of GSH concentrations and GPx activity. Hcit with hyperammonemia (urease treatment) decreased TAS and CAT activity. We also showed that urease treatment per se was able to enhance TBA-RS levels. Finally, nitric oxide production was not altered by Orn and Hcit alone or in combination with hyperammonemia. Our data indicate that the major metabolites accumulating in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome provoke lipid and protein oxidative damage and a reduction of the antioxidant defenses in the brain. Therefore, it is presumed that oxidative stress may represent a relevant pathomechanism involved in the brain damage found in patients affected by this disease. 相似文献
26.
Natacha Brunelle Karine Bertrand Isabelle Beaudoin Cinthia Ledoux Annie Gendron Catherine Arseneault 《Journal of adolescence》2013,36(4):705-716
Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency. 相似文献
27.
Vincent Degos MD PhD Stéphane Peineau PhD Cora Nijboer PhD Angela M. Kaindl MD PhD Stéphanie Sigaut MD Géraldine Favrais MD PhD Frank Plaisant MD PhD Natacha Teissier MD PhD Elodie Gouadon PhD Alain Lombet PhD Elie Saliba MD PhD Graham L. Collingridge PhD Mervyn Maze MB ChB Ferdinando Nicoletti Cobi Heijnen PhD Jean Mantz MD PhD Annemieke Kavelaars PhD Pierre Gressens MD PhD 《Annals of neurology》2013,73(5):667-678
28.
29.
Sarra Smati MD Blandine Tramunt MD Matthieu Wargny MD Cyrielle Caussy MD Bénédicte Gaborit MD Camille Vatier MD Bruno Vergès MD Deborah Ancelle MD Coralie Amadou MD Leila A. Bachir MD Olivier Bourron MD Christine Coffin-Boutreux MD Sara Barraud MD Anne Dorange MD Bénédicte Fremy MD Jean-François Gautier MD Natacha Germain MD Etienne Larger MD Stéphanie Laugier-Robiolle MD Laurent Meyer MD Arnaud Monier MD Isabelle Moura MD Louis Potier MD Nadia Sabbah MD Dominique Seret-Bégué MD Patrice Winiszewski MD Matthieu Pichelin PharmD Pierre-Jean Saulnier MD Samy Hadjadj MD Bertrand Cariou MD Pierre Gourdy MD for the CORONADO investigators 《Diabetes, obesity & metabolism》2021,23(2):391-403
30.
Christophe Van Dijck Achilleas Tsoumanis Anke Rotsaert Bea Vuylsteke Dorien Van den Bossche Elke Paeleman Irith De Baetselier Isabel Brosius Jolein Laumen Jozefien Buyze Kristien Wouters Lutgarde Lynen Marjan Van Esbroeck Natacha Herssens Said Abdellati Steven Declercq Thijs Reyniers Yven Van Herrewege Chris Kenyon 《The Lancet infectious diseases》2021,21(5):657-667