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Sonia Franciosi PhD Yaein Shim BSc Margaret Lau BCom Michael R. Hayden MB ChB PhD Blair R. Leavitt MD CM 《Movement disorders》2013,28(14):1987-1994
Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre‐ to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre‐far, pre‐close, early, mild, moderate, and severe HD stages. A fixed‐effect meta‐analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre‐ and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross‐sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK‐HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta‐analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications . © 2013 International Parkinson and Movement Disorder Society 相似文献
74.
Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis 下载免费PDF全文
Ward KN Leong HN Thiruchelvam AD Atkinson CE Clark DA 《Journal of clinical microbiology》2007,45(4):1298-1304
The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6 immunoglobulin G antibody was measured by indirect immunofluorescence. Primary infection was defined by antibody seroconversion and/or a low concentration of HHV-6 DNA (<3.0 log(10) copies/ml) in a seronegative serum. Chromosomal integration was defined by a high concentration of viral DNA in serum (>/=3.5 log(10) copies/ml) or whole blood (>/=6.0 log(10) copies/ml). The prevalences of CSF HHV-6 DNA in primary infection and chromosomal integration were 2.5% and 2.0%, respectively, in the young children (<2 years) and 0% and 1.3%, respectively, in the older children and/or adults. The mean concentration of CSF HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was significantly lower than that of 21 patients with viral chromosomal integration (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas in viral integration, 4 patients had HHV-6A and 17 patients HHV-6B. Apart from primary infection, chromosomal integration is the most likely cause of HHV-6 DNA in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6 encephalitis or other type of active central nervous system infection should not be made without first excluding chromosomal HHV-6 integration by measuring DNA load in CSF, serum, and/or whole blood. 相似文献
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Min Soo Choo Sung Yong Cho Kyungtae Ko Chang Wook Jeong Seung Bae Lee Ja Hyeon Ku Sung Kyu Hong Seok-Soo Byun Cheol Kwak Hyeon Hoe Kim Sang Eun Lee Hyeon Jeong 《World journal of urology》2014,32(6):1401-1409
Purpose
We investigated the influence of positive surgical margins (PSMs) and their locations on biochemical recurrence (BCR) according to risk stratification and surgical modality.Methods
A total of 1,874 post-radical-prostatectomy (RP) patients of pT2–T3a between 2000 and 2010 at three tertiary centers, and who did not receive neoadjuvant/adjuvant therapy, were included in this study. Patients were stratified according to BCR risk: low risk (PSA <10, pT2a-b, and pGS ≤6), intermediate risk (PSA 10–20 and/or pT2c and/or pGS 7), and high risk (PSA >20 or pT3a or pGS 8–10). The median follow-up was 43 months.Results
PSMs were a significant predictor of BCR in both the intermediate- and high-risk-disease groups (P = .001, HR 2.1, 95 % CI 1.3–3.4; P < .001, HR 2.8, 95 % CI 2.0–4.1). Positive apical margin was a significant risk factor for BCR in high-risk disease (P = .003, HR 2.0, 95 % CI 1.2–3.3), but not in intermediate-risk disease (P = .06, HR 1.7, 95 % CI 0.9–3.1). Positive bladder neck margin was a significant risk factor for BCR in both intermediate- and high-risk disease (P < .001, HR 5.4, 95 % CI 2.1–13.8; P = .001, HR 4.5, 95 % CI 1.8–11.4). In subgroup analyses, robotic RP provided comparable BCR-free survival regardless of risk stratification. Patients with PSMs showed similar BCR-free survival between open and robotic RP (log-rank, P = .897).Conclusions
Post-RP PSMs were a significantly independent predictor of disease progression in high-risk disease as well as intermediate-risk disease. Both positive apical and bladder neck margins are also significant risk factors of BCR in high-risk disease. Patients with PSMs showed similar BCR-free survival between open and robotic surgery. 相似文献77.
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Andre C. Felicio MD PhD Katherine Dinelle MSc Pankaj A. Agarwal MD DNB DM Jessamyn McKenzie LPN Nicole Heffernan RN Jeremy D. Road MD Silke Appel‐Cresswell MD Zbigniew K. Wszolek MD Matthew J. Farrer PhD Michael Schulzer MD PhD Vesna Sossi PhD A. Jon Stoessl CM MD FRCPC 《Movement disorders》2014,29(9):1197-1201
79.
Kyung Chul Moon MD PhD Myong Kim MD Cheol Kwak MD PhD Hyeon Hoe Kim MD PhD Ja Hyeon Ku MD PhD 《Annals of surgical oncology》2014,21(9):3132-3141
Purpose
The objective of the study was to validate the previously reported lookup Table and Bladder Cancer Research Consortium (BCRC) nomogram in predicting cancer-specific mortality (CSM) and all-cause mortality (ACM) after radical cystectomy using an external cohort from South Korea.Methods
The study comprised 409 patients. Discrimination was quantified with the concordance index. The relationship between the model-derived and actual CSM and ACM was graphically explored within calibration plots. Clinical net benefit was evaluated by decision curve analysis.Results
Of the 409 patients, 147 (35.9 %) had died from various causes. One hundred two deaths were attributable to bladder cancer. For CSM at 5 years, the bootstrap-corrected concordance indices of the American Joint Committee on Cancer (AJCC) staging system, lookup Table, and BCRC nomogram were 71.8 % (95 % confidence interval [CI] 66.9–76.5), 73.0 % (95 % CI 67.9–78.0), and 76.2 % (95 % CI 71.6–80.9), respectively. For ACM at the same time point, the discrimination accuracies of these models were 70.7 % (95 % CI 66.7–74.6), 72.8 % (95 % CI 68.5–76.9), and 76.2 % (95 % CI 72.3–80.2), respectively. The calibration plots tended to exaggerate both survival outcomes in all models. When compared to the lookup Table as well as the AJCC staging system, the BCRC nomogram performed well across a wide range of threshold probabilities using decision curve analysis.Conclusions
The BCRC nomogram was characterized by higher accuracy and larger potential clinical benefit compared to the lookup Table. However, there is a great need for additional models that consider outcomes of patients for whom the existing models do not apply. 相似文献80.
Susan Hoe James W. Ivey Mohammed A. Boraey Abouzar Shamsaddini-Shahrbabak Emadeddin Javaheri Sadaf Matinkhoo Warren H. Finlay Reinhard Vehring 《Pharmaceutical research》2014,31(2):449-465