首页 | 官方网站   微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1648篇
  免费   130篇
  国内免费   8篇
医药卫生   1786篇
  2023年   16篇
  2022年   52篇
  2021年   114篇
  2020年   62篇
  2019年   107篇
  2018年   112篇
  2017年   53篇
  2016年   62篇
  2015年   61篇
  2014年   98篇
  2013年   90篇
  2012年   169篇
  2011年   150篇
  2010年   63篇
  2009年   60篇
  2008年   75篇
  2007年   92篇
  2006年   72篇
  2005年   65篇
  2004年   46篇
  2003年   38篇
  2002年   39篇
  2001年   13篇
  2000年   4篇
  1999年   3篇
  1998年   4篇
  1997年   3篇
  1996年   4篇
  1995年   7篇
  1994年   2篇
  1993年   2篇
  1992年   3篇
  1991年   3篇
  1990年   2篇
  1989年   3篇
  1987年   4篇
  1986年   4篇
  1983年   2篇
  1982年   4篇
  1981年   3篇
  1980年   1篇
  1979年   3篇
  1978年   1篇
  1977年   2篇
  1976年   3篇
  1975年   1篇
  1973年   3篇
  1972年   1篇
  1969年   1篇
  1968年   1篇
排序方式: 共有1786条查询结果,搜索用时 15 毫秒
21.
The four clinical features of spondyloarthropathy, i.e. axial involvement, peripheral articular involvement, enthesopathy and extra-articular features, must be assessed in each patient suffering from spondyloarthropathy at each visit.The ASsessment in Ankylosing Spondylitis working group is establishing recommendations to facilitate the short- and long-term monitoring of patients suffering from spondyloarthropathies.Several relevant instruments are available for assessing the main domains, allowing evaluation of such patients - for example, pain, functional disability and spinal mobility. Other investigations are required in order to obtain relevant instruments for other domains, such as structural severity.  相似文献   
22.
Familial and genetic aspects of spondyloarthropathy   总被引:5,自引:0,他引:5  
Predisposition to SpA is largely determined by genetic factors including HLA-B27 and other as yet unknown genes that might be tracked by a positional cloning approach. Analysis performed on a large cohort of SpA multiplex families revealed that the different articular and extra-articular inflammatory manifestations comprising the SpA spectrum were linked together, implying that they were determined by a shared set of factors, including HLA-B27. The variety of phenotypes appeared to be related to ubiquitous and secondary factors. Hence, SpA appeared to be more homogenous than previously thought and should be regarded as a unique disease. This conclusion also implies that genetic studies should be performed on the whole group. Such an approach allowed identification of HLA-DR4 as a gene contributing to SpA predisposition independently of linkage disequilibrium with HLA-B27. A significant role for CARD15/NOD2 gene in predisposition to SpA was ruled out, in agreement with the hypothesis that the inflammatory bowel disease in SpA is determined by factors different than those responsible for isolated Crohn's disease.  相似文献   
23.
In contrast to rheumatoid arthritis (RA), the concept of disease modification in ankylosing spondylitis (AS) remains to be clarified. Endpoint measures employed in AS trials primarily assess features related to symptomatology while endpoints considered more relevant to the concept of disease modification, such as spinal mobility, acute-phase reactants and radiological progression, either lack sensitivity to change or have not been comprehensively validated. NSAIDs alleviate symptoms of AS but most trials have been short term, precluding meaningful conclusions regarding disease modification. Among disease-modifying therapies used in RA, sulfasalazine has been studied in several controlled trials mostly in patients with longstanding disease, effect sizes being small and limited to those with peripheral synovitis. No conclusions can be drawn from the limited studies evaluating methotrexate.  相似文献   
24.
25.
26.
Classification of rare missense substitutions observed during genetic testing for patient management is a considerable problem in clinical genetics. The Bayesian integrated evaluation of unclassified variants is a solution originally developed for BRCA1/2. Here, we take a step toward an analogous system for the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) that confer colon cancer susceptibility in Lynch syndrome by calibrating in silico tools to estimate prior probabilities of pathogenicity for MMR gene missense substitutions. A qualitative five‐class classification system was developed and applied to 143 MMR missense variants. This identified 74 missense substitutions suitable for calibration. These substitutions were scored using six different in silico tools (Align‐Grantham Variation Grantham Deviation, multivariate analysis of protein polymorphisms [MAPP], MutPred, PolyPhen‐2.1, Sorting Intolerant From Tolerant, and Xvar), using curated MMR multiple sequence alignments where possible. The output from each tool was calibrated by regression against the classifications of the 74 missense substitutions; these calibrated outputs are interpretable as prior probabilities of pathogenicity. MAPP was the most accurate tool and MAPP + PolyPhen‐2.1 provided the best‐combined model (R2 = 0.62 and area under receiver operating characteristic = 0.93). The MAPP + PolyPhen‐2.1 output is sufficiently predictive to feed as a continuous variable into the quantitative Bayesian integrated evaluation for clinical classification of MMR gene missense substitutions.  相似文献   
27.
28.
OBJECTIVE: To assess the prevalence and severity of peripheral enthesitis among the different subtypes of spondylarthropathy (SpA) by using ultrasonography (US) in B mode with power Doppler. METHODS: One hundred sixty-four consecutive patients with SpA (according to the criteria of the European Spondylarthropathy Study Group) and 64 control patients (34 with mechanical low back pain [MBP] and 30 with rheumatoid arthritis [RA]) underwent US examination of major entheses of their limbs. Particular attention was given to the detection of vascularization at the following sites: cortical bone insertion of entheses, junction between tendon and entheses, body of tendon, and bursa. RESULTS: Abnormal US findings consistent with at least one enthesitis were observed in 161 of 164 SpA patients (98%), affecting 1,131 of 2,952 entheses examined (38%). In contrast, only 132 of 1,152 entheses (11%) were found to be abnormal in 33 of 64 control patients (52%). US enthesitis was most commonly distributed in the distal portion of the lower limbs, irrespective of SpA subtype and of skeletal distribution of clinical symptoms. None of the abnormal entheses in control patients showed vascularization, compared with 916 of 1,131 abnormal entheses in SpA patients (81%), where it was always detected at the cortical bone insertion and sometimes also in the bursa. In SpA patients, the US pattern depended on the clinical presentation, with a higher prevalence of the most severe stages in those with peripheral forms. CONCLUSION: US in B mode combined with power Doppler allowed the detection of peripheral enthesitis in a majority of SpA patients, but not in MBP or RA patients. The presence of entheseal involvement was independent of SpA subtype, but its degree of severity appeared to be greater in peripheral forms. US could be very useful for both the diagnosis and the assessment of SpA activity.  相似文献   
29.
OBJECTIVE: To determine prognostic factors of disability in early rheumatoid arthritis (RA) and to investigate the radiological and functional course of the disease. METHODS: A total of 191 patients with early RA (diagnosed for less than one year) according to American College of Rheumatology criteria were followed prospectively for 5 years. At baseline and at endpoint, Stanford Health Assessment Questionnaire (HAQ) scores and radiological scores (Sharp's score modified by van der Heijde) were performed. Correlations between numerous baseline data and HAQ score at endpoint were analyzed, using nonparametric tests. A multilinear regression model was performed to select independent prognostic factors of HAQ disability. RESULTS: During the 5-year followup, mean HAQ decreased from 1.3 (+/- 0.7) to 0.6 (+/- 0.6). There were 98 (65.3%) patients with a score > 1 point at baseline, but only 46 (27.4%) after 3 years and 34 (21.8%) after 5 years. Moreover, 90% of the patients had an improvement of the disability score. Final HAQ disability was associated with baseline values of HAQ score, Pain, Ritchie index, tender joint count, Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and erosion. Multivariate analysis selected baseline HAQ score, Ritchie index, ESR, CRP, and presence of erosion as independent prognostic factors of HAQ disability. The probability cutoff in the logistic model was selected to minimize the sum of false positive and false negative values: negative predictive value = 92.71%, positive predictive value = 46.15%, p = 0.408. Sex, age, IgM and IgA rheumatoid factors, other tested autoantibodies, and HLA class II genes did not contribute significantly to prediction of the disability after 5 years. At baseline, mean scores were 3.6 units (+/- 7.7) for total radiological score, 1.7 (+/- 4.5) for erosion score, and 1.9 (+/- 3.7) for joint space narrowing score. After 5 years, they were 17.9 +/- 22.3, 6.9 +/- 9.5, and 11.0 +/- 15.4, respectively. No erosion was present at the start in 58.0% of patients, compared to 24.2% and 22.4% at 3 and 5 years. Global radiographic progression concerned 87 patients (55.8%) during the 5 years. CONCLUSION: During the first 5 years of RA, radiological damage increased progressively in half of the patients, whereas HAQ disability improved in most of them during the same period of time and could be predicted by baseline values of HAQ score, Ritchie index, ESR, CRP, and presence (or absence) of erosion.  相似文献   
30.
OBJECTIVE: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here. METHODS: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter. All adverse events were documented. Efficacy variables were the European League Against Rheumatism (EULAR) response criteria using the Disease Activity Score (DAS 28) responder rate and the response rate according to American College of Rheumatology (ACR) criteria. At Week 24, baseline data were analyzed to determine predictive factors for treatment response. RESULTS: A total of 969 patients were entered in the trial. No adverse events that have not previously been seen with leflunomide were reported. Among 968 evaluable patients, 673 (69.6%) completed 24 weeks of treatment and were responders according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of treatment and were responders according to ACR 20%. Thus, there was a high correlation between the EULAR and ACR criteria in determining treatment response. In addition, 240 (24.8%) patients had a low DAS 28 (< or = 3.2) and 123 (12.7%) patients fulfilled the disease remission criteria (DAS 28 < 2.6) at the end of the study. CONCLUSION: This study demonstrates that leflunomide is well tolerated, with a safety profile similar to that seen previously in Phase III studies, and confirms the efficacy of leflunomide across a range of patient categories.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号-23

京公网安备 11010802026262号