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61.
62.
Vilde D. Haakensen Anand Khadse Vandana Sandhu Ann Rita Halvorsen Steinar K. Solberg Lars H. Jørgensen Odd Terje Brustugun Elin H. Kure Åslaug Helland 《International journal of cancer. Journal international du cancer》2020,147(10):2957-2966
Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild-type samples and a 17%-fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes. 相似文献
63.
Mai Tone Lønnebakken M.D. † Øyvind Bleie M.D. Elin Strand M.Sc. † Eva M. Staal Ph.D. † Ottar K. Nygård Ph.D. † Eva Gerdts Ph.D. † 《Echocardiography (Mount Kisco, N.Y.)》2009,26(1):52-60
Background: Myocardial contrast stress echocardiography (stress MCE) is a novel method for diagnosing coronary artery disease (CAD). Few studies have compared the diagnosis of ischemia by stress MCE to angiographic CAD. Methods: Dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 37 patients (8 women) aged 45–75 years with symptomatic CAD and at least one significant coronary artery stenosis measured by quantitative coronary angiography (QCA). The total and regional perfusion and wall motion (WM) were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 17-segment left ventricular model. Results: An intermediate stress level was obtained in 29 (78%) patients, and 2 (5%) patients obtained peak stress. A perfusion defect was detected in 92% and WM abnormality in 57% of the patients at peak stress (P < 0.01). By perfusion, 70% of stenoses were both detected and correctly anatomically located, compared to 42% by WM (P < 0.01). All 21 patients with multivessel disease and/or proximal left anterior descending (LAD) stenosis measured by QCA were identified by stress-induced perfusion defects, while only 11 of them were identified by WM abnormalities (P < 0.01). Conclusion: Perfusion scoring is superior to WM scoring during stress MCE for diagnosing significant CAD in patients obtaining intermediate stress level, in particular, when multivessel disease or proximal LAD stenosis is present. 相似文献
64.
Leslie Calapre Elin S. Gray Sandrine Kurdykowski Anthony David Pascal Descargues Mel Ziman 《BMC dermatology》2017,17(1):8
Background
Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.Results
Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.Conclusion
This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat65.
66.
Elin M. Svensson Francesca Aweeka Jeong-Gun Park Florence Marzan Kelly E. Dooley Mats O. Karlsson 《Antimicrobial agents and chemotherapy》2013,57(6):2780-2787
Safe, effective concomitant treatment regimens for tuberculosis (TB) and HIV infection are urgently needed. Bedaquiline (BDQ) is a promising new anti-TB drug, and efavirenz (EFV) is a commonly used antiretroviral. Due to EFV''s induction of cytochrome P450 3A4, the metabolic enzyme responsible for BDQ biotransformation, the drugs are expected to interact. Based on data from a phase I, single-dose pharmacokinetic study, a nonlinear mixed-effects model characterizing BDQ pharmacokinetics and interaction with multiple-dose EFV was developed. BDQ pharmacokinetics were best described by a 3-compartment disposition model with absorption through a dynamic transit compartment model. Metabolites M2 and M3 were described by 2-compartment models with clearance of BDQ and M2, respectively, as input. Impact of induction was described as an instantaneous change in clearance 1 week after initialization of EFV treatment and estimated for all compounds. The model predicts average steady-state concentrations of BDQ and M2 to be reduced by 52% (relative standard error [RSE], 3.7%) with chronic coadministration. A range of models with alternative structural assumptions regarding onset of induction effect and fraction metabolized resulted in similar estimates of the typical reduction and did not offer a markedly better fit to data. Simulations to investigate alternative regimens mitigating the estimated interaction effect were performed. The results suggest that simple adjustments of the standard regimen during EFV coadministration can prevent reduced exposure to BDQ without increasing exposures to M2. However, exposure to M3 would increase. Evaluation in clinical trials of adjusted regimens is necessary to ensure appropriate dosing for HIV-infected TB patients on an EFV-based regimen. 相似文献
67.
Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults
Maria Kakoulidou Hanna Ingelman-Sundberg Elin Johansson Alberto Cagigi Salah Eldin Farouk Anna Nilsson Kari Johansen 《Vaccine》2013
The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination. 相似文献
68.
Anners Lerdal Britt Moe Elin Digre Thomas Harding Frode Kristensen Ellen K. Grov Linda N. Bakken Marthe L. Eklund Ireen Ruud & Joseph S. Rossi 《Journal of advanced nursing》2009,65(1):193-202
Title. Stages of Change – Continuous Measure (URICA-E2): psychometrics of a Norwegian version.
Aim. This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA-E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change.
Background. While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature.
Method. Cross-sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA-E2 was translated into Norwegian according to standardized procedures.
Findings. Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non-Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour.
Conclusion. The URICA-E2 was for the most part replicated from Reed's original work. The result of the cluster analysis of the items associated with the factor 'Action' suggests that these do not adequately measure the factor. 相似文献
Aim. This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA-E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change.
Background. While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature.
Method. Cross-sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA-E2 was translated into Norwegian according to standardized procedures.
Findings. Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non-Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour.
Conclusion. The URICA-E2 was for the most part replicated from Reed's original work. The result of the cluster analysis of the items associated with the factor 'Action' suggests that these do not adequately measure the factor. 相似文献
69.
Objective.— The objective of this study was to compare the relationship between repeated momentary reports of stress and headaches in female adolescents with varying degrees of headache frequency. Background.— Headaches are the most common form of pain reported by adolescents affecting more than a third of all adolescents. High levels of stress during adolescence may predispose an adolescent to experience headaches in adulthood. Randomized, momentary data collection of stress and headaches provides the most accurate data regarding the adolescent experience of these variables. Methods.— The research methodology, ecological momentary assessment, is a valid approach to better understand the relationship between stress and headaches in adolescence. Data were obtained by each participant's use of an electronic diary (ED), which captured repeated momentary reports of perceived stress, head pain, and stress‐related symptoms in female adolescents with varying degrees of recurrent headache. Seven times per day for the 21‐day study period, teen girls responded to ED questions about their current stress levels, head pain, and stress‐related symptoms. Based on participants' momentary reports of headaches, Low Headache, Moderate Headache, and Chronic Headache groups were created. General estimating equation models were used to analyze the relationship between momentary variables as well as the lag effect between stress and head pain. Results.— Thirty‐one participants, aged 14‐18 years, completed 2841 randomized ED reports and reported 674 occurrences of headache. The Chronic Headache and Moderate Headache groups reported significantly increased levels of stress, head pain, and headaches. The relationship between momentary stress and head pain was significantly strong both within and across participants. The strength of this relationship increased with increased headache activity. A significant lag effect was found between stress and headaches; however, the effect of depression as a moderator of the stress and headache relationship remains unclear. Conclusion.— Perceived stress and head pain was highly correlated in these female adolescents. Given the large population of teens affected by headaches, a plausible next step would be to validate these results in other samples and to determine methods with which to identify teens who may be at risk for a pattern of increasing stress and headaches. 相似文献
70.