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1.
The Role of APO-1-Mediated Apoptosis in the Immune System 总被引:12,自引:0,他引:12
2.
Kirstin Vach Ali Al-Ahmad Annette Anderson Johan Peter Woelber Lamprini Karygianni Annette Wittmer Elmar Hellwig 《Nutrients》2021,13(3)
Background: Investigating the influence of nutrition on oral health has a long scientific history. Due to recent technical advances like sequencing techniques for the oral microbiota, this topic has gained scientific interest again. A basic challenge is to understand the influence of nutrition on the oral microbiota and on the interaction between the oral bacteria, which is also statistically challenging. Methods: Log-transformed ratios of two bacteria concentrations are introduced as the basic analytic tool. The framework is illustrated by application in an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Results: The method could be sufficiently used to analyse the interrelation between the bacteria and to identify some bacterial groups with the same as well as different reactions to additional dietary components. It was found that the strongest changes in bacterial concentrations were achieved by the additional consumption of dairy products. Conclusion: A log ratio-based analysis offers insights into the relation of different bacteria while taking specific features of compositional data into account. The presented methods allow becoming independent of the behaviour of other bacteria, which is a disadvantage of common analysis methods of compositions. The results indicate that modulations of the oral biofilm microbiota due to nutrition change can be attained. 相似文献
3.
Clephane Kirstin Sartin-Tarm Anneliis Lorenz Tierney K. 《Archives of sexual behavior》2022,51(2):737-742
Archives of Sexual Behavior - 相似文献
4.
5.
Hunter Theresa Grabner Michael Birt Julie Isenberg Keith Shan Mingyang Teng Chia-Chen Wu Jianmin Griffing Kirstin Lisse Jeffrey Curtis Jeffrey R. 《Clinical rheumatology》2022,41(9):2863-2874
Clinical Rheumatology - This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis... 相似文献
6.
7.
Anthonie W. A. Lensing Christoph Male Guy Young Dagmar Kubitza Gili Kenet M. Patricia Massicotte Anthony Chan Angelo C. Molinari Ulrike Nowak-Goettl Ákos F. Pap Ivet Adalbo William T. Smith Amy Mason Kirstin Thelen Scott D. Berkowitz Mark Crowther Stephan Schmidt Victoria Price Martin H. Prins Paul Monagle 《Thrombosis journal》2018,16(1):34
Background
Venous thromboembolism (VTE) is a relatively rare condition in childhood with treatment mainly based on extrapolation from studies in adults. Therefore, clinical trials of anticoagulation in children require novel approaches to deal with numerous challenges. The EINSTEIN-Jr program identified pediatric rivaroxaban regimens commencing with in vitro dose finding studies followed by evaluation of children of different ages through phase I and II studies using extensive modeling to determine bodyweight-related doses. Use of this approach resulted in drug exposure similar to that observed in young adults treated with rivaroxaban 20?mg once-daily.Methods
EINSTEIN-Jr phase III is a randomized, open-label, study comparing the efficacy and safety of rivaroxaban 20?mg-equivalent dose regimens with those of standard anticoagulation for the treatment of any types of acute VTE in children aged 0–18?years.A total of approximately 500 children are expected to be included during the 4-year study window. Flexibility of treatment duration is allowed with study treatment to be given for 3?months with the option to continue treatment in 3-month increments, up to a total of 12?months. However, based on most common current practice, children younger than 2?years with catheter-related thrombosis will have a main treatment period of 1?month with the option to prolong treatment in 1-month increments, up to a total of 3?months.Conclusions
EINSTEIN-Jr will compare previously established 20?mg-equivalent rivaroxaban dosing regimens with standard anticoagulation for the treatment of VTE in children. Demonstration of similarity of disease, as well as equivalent rivaroxaban exposure and exposure-response will enable extrapolation of efficacy from adult trials, which is critical given the challenges of enrollment in pediatric anticoagulation trials.Trial registration
Clinicaltrials.gov NCT02234843, registered on 9 September 2014.8.
Stefan Willmann Kirstin Thelen Dagmar Kubitza Anthonie W. A. Lensing Matthias Frede Katrin Coboeken Jan Stampfuss Rolf Burghaus Wolfgang Mück Jörg Lippert 《Thrombosis journal》2018,16(1):32
Background
The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg once-daily dose for adults. A physiologically based pharmacokinetic (PBPK) model for pediatric rivaroxaban dosing has been constructed.Methods
We quantitatively assessed the pharmacokinetics (PK) of a single rivaroxaban dose in children using population pharmacokinetic (PopPK) modelling and assessed the applicability of the PBPK model. Plasma concentration–time data from the EINSTEIN-Jr phase I study were analysed by non-compartmental and PopPK analyses and compared with the predictions of the PBPK model. Two rivaroxaban dose levels, equivalent to adult doses of rivaroxaban 10 mg and 20 mg, and two different formulations (tablet and oral suspension) were tested in children aged 0.5–18 years who had completed treatment for VTE.Results
PK data from 59 children were obtained. The observed plasma concentration–time profiles in all subjects were mostly within the 90% prediction interval, irrespective of dose or formulation. The PopPK estimates and non-compartmental analysis-derived PK parameters (in children aged ≥6 years) were in good agreement with the PBPK model predictions.Conclusions
These results confirmed the applicability of the rivaroxaban pediatric PBPK model in the pediatric population aged 0.5–18 years, which in combination with the PopPK model, will be further used to guide dose selection for the treatment of VTE with rivaroxaban in EINSTEIN-Jr phase II and III studies.9.
Dagmar Kubitza Stefan Willmann Michael Becka Kirstin Thelen Guy Young Leonardo R. Brandão Paul Monagle Christoph Male Anthony Chan Gili Kennet Ida Martinelli Paola Saracco Anthonie W. A. Lensing 《Thrombosis journal》2018,16(1):31