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排序方式: 共有1880条查询结果,搜索用时 15 毫秒
71.
Ahmed ElBoraie JulieAnne Tanner Andy Z.X. Zhu Katrina G. Claw Bhagwat Prasad Erin G. Schuetz Kenneth E. Thummel Koya Fukunaga Taisei Mushiroda Michiaki Kubo Neal L. Benowitz Caryn Lerman Rachel F. Tyndale 《CTS Clinical and Translational Science》2022,15(1):204
CYP2A6 activity, phenotyped by the nicotine metabolite ratio (NMR), is a predictor of several smoking behaviors, including cessation and smoking‐related disease risk. The heritability of the NMR is 60–80%, yet weighted genetic risk scores (wGRSs) based on common variants explain only 30–35%. Rare variants (minor allele frequency <1%) are hypothesized to explain some of this missing heritability. We present two targeted sequencing studies where rare protein‐coding variants are functionally characterized in vivo, in silico, and in vitro to examine this hypothesis. In a smoking cessation trial, 1687 individuals were sequenced; characterization measures included the in vivo NMR, in vitro protein expression, and metabolic activity measured from recombinant proteins. In a human liver bank, 312 human liver samples were sequenced; measures included RNA expression, protein expression, and metabolic activity from extracted liver tissue. In total, 38 of 47 rare coding variants identified were novel; characterizations ranged from gain‐of‐function to loss‐of‐function. On a population level, the portion of NMR variation explained by the rare coding variants was small (~1%). However, upon incorporation, the accuracy of the wGRS was improved for individuals with rare protein‐coding variants (i.e., the residuals were reduced), and approximately one‐third of these individuals (12/39) were re‐assigned from normal to slow metabolizer status. Rare coding variants can alter an individual’s CYP2A6 activity; their integration into wGRSs through precise functional characterization is necessary to accurately assess clinical outcomes and achieve precision medicine for all. Investigation into noncoding variants is warranted to further explain the missing heritability in the NMR. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
72.
Prognostic value of circulating pregnancy-associated plasma protein levels in patients with chronic stable angina. 总被引:7,自引:0,他引:7
Ahmad A Elesber Cheryl A Conover Ali E Denktas Ryan J Lennon David R Holmes Michael T Overgaard Michael Christiansen Claus Oxvig Lilach O Lerman Amir Lerman 《European heart journal》2006,27(14):1678-1684
AIMS: Unstable coronary atherosclerotic plaque can be present in patients with chronic stable coronary artery disease (CAD). Our objective was to assess whether measurement of plasma pregnancy-associated plasma protein (PAPP-A) level, a reflection of plaque instability, in patients with chronic stable CAD had an independent prognostic value on the subsequent incidence of death, acute coronary syndrome (ACS), and revascularization. METHODS AND RESULTS: Patients referred for coronary angiography were recruited. A cohort of 103 patients with stable symptoms for at least 6 weeks and with a coronary angiogram showing at least a 50% luminal diameter narrowing formed our study population. Median follow-up was 4.9 years. Mean age was 65+/-10 years. In a multivariable model that included CAD traditional risk factors, ejection fraction, extent of coronary atherosclerosis, prior history of myocardial infarction, prior revascularization, discharge medications, and C-reactive protein, the plasma PAPP-A was found to be significantly associated with the endpoint of future death [adjusted hazard ratio (HR) 5.29; 95% CI 1.27-22.0; P=0.023] and with the endpoint of future death and ACS (adjusted HR 3.56; 95% CI 1.27-10.0; P=0.015), but not with the endpoint of future death and revascularization. CONCLUSION: Measurement of plasma PAPP-A level in patients with chronic stable CAD has an independent prognostic value on the occurrence of death and ACS. 相似文献
73.
Malignant involvement of the spine: assessment by 18F-FDG PET/CT. 总被引:11,自引:0,他引:11
Ur Metser Hedva Lerman Annat Blank Gennady Lievshitz Felix Bokstein Einat Even-Sapir 《Journal of nuclear medicine》2004,45(2):279-284
The purpose of the study was to assess the role of (18)F-FDG PET/CT in the assessment of secondary malignant involvement of the spinal column. METHODS: In 51 patients, 242 lesions at the spinal region detected on (18)F-FDG PET/CT were interpreted separately on PET, CT, and fused PET/CT images, including differentiation between benign and malignant lesions and the level in the vertebral column. CT evaluation also included the type of bony lesion (osteolytic, osteoblastic, or mixed) and accompanying soft-tissue abnormalities; for example, epidural masses and tumor involvement of the neural foramina. RESULTS: Of the 242 lesions detected on PET/CT, PET alone identified 220 lesions and CT alone identified 159; 217 (90%) were malignant and 25 benign. (18)F-FDG PET alone detected significantly more malignant lesions than did CT alone (96% vs. 68%, respectively, P < 0.001). The specificity was 56% for both PET alone and CT alone. PET alone was incorrect in determining the level of abnormality within the vertebral column in 33 (15%) lesions and in determining the part of the vertebra involved in 40 (18%) lesions. In 17 (33%) patients, either epidural extension of tumor (n = 7 lesions), neural foramen involvement of tumor (n = 7 lesions), or a combination of both (n = 11 lesions) was detected. On a patient-based analysis, the sensitivity of PET and of PET/CT for the detection of spinal metastasis was 98% and 74%, respectively (P < 0.01). CONCLUSION: (18)F-FDG PET/CT has better specificity for detection of malignant involvement of the spine than does (18)F-FDG PET. It allows for precise localization of lesions and identifies accompanying soft-tissue involvement, which is of potential neurologic significance. 相似文献
74.
Caryn E. Peterson Rebecca L. Sedjo Faith G. Davis Craig A. Beam Anna R. Giuliano 《Nutrition and cancer》2013,65(6):728-733
Persistent infection with human papillomavirus (HPV) is the primary etiologic factor for cervical cancer. The synergistic effect of carotenoids on HPV persistence has not been examined. To explore these potential synergies, we developed 2 measures of carotenoid status using circulating and dietary intake nutrients in which each nutrient was given equal weighting. We then compared persistent HPV infection with its counterpart, intermittent infection. In the analysis using the Crude Index, no association was observed between circulating nutrients and persistent infection with oncogenic HPV [odds ratio (OR)adjusted = 0.8, 95% confidence interval (CI) = 0.3–2.2)] or any type HPV (ORadjusted = 0.8, 95% CI = 0.3–2.1). Similar results were obtained using the Cumulative Index. However, associations between dietary intake and persistent infection were observed using both indexes. When the analysis was restricted to oncogenic HPV, a 50% higher risk was observed for women with low dietary carotenoid status using the Crude Index (ORadjusted = 1.5, 95% CI = 0.6–3.7). In the analysis using any type HPV, the adjusted OR for women with low dietary intake of combined carotenoids using the Cumulative Index was 2.4 (95% CI = 1.1–5.2). These results may be consistent with the hypothesis that low levels of carotenoids may increase the risk of persistent HPV infection. 相似文献
75.
David P King Sara Paciga Eve Pickering Neal L Benowitz Laura J Bierut David V Conti Jaakko Kaprio Caryn Lerman Peter W Park 《Neuropsychopharmacology》2012,37(3):641-650
Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9–12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23–2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27–2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36–0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45–2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions. 相似文献
76.
77.
Ethnic differences in risk perception among women at increased risk for breast cancer 总被引:6,自引:0,他引:6
Chanita Hughes M.S. Caryn Lerman Ph.D. Edward Lustbader Ph.D. 《Breast cancer research and treatment》1996,40(1):25-35
Summary There has been increasing interest in the role of cultural and ethnic factors in breast cancer risk perceptions and screening practices. This study examined ethnic differences in breast cancer risk perception in 112 African American and 224 white women ages 35 and older who had at least one first-degree relative diagnosed with breast cancer. These samples were matched for education and age. Data on breast cancer risk factors, risk perceptions, breast cancer worries, and breast cancer screening practices were collected through structured telephone interviews. The results show that African American women were significantly less likely than white women to report heightened perceptions of personal risk after their relative was diagnosed with breast cancer (61% vs 82%; p<.001). Despite this, African American women had significantly greater concerns about their personal risk of breast cancer and worries about their affected relative. African American women also scored significantly higher than white women on a measure of avoidance of breast cancer-related thoughts and feelings. These psychological variables were associated independently with breast cancer risk perception in multivariate models, taking precedence over demographic and risk factor predictors. Observed ethnic differences in breast cancer risk perceptions and psychological distress may be attributable to the influence of cultural factors particular to people of African descent, such as the importance of interpersonal relationships, spirituality, and time orientation. An Africentric perspective is used to interpret these findings and to provide suggestions for delivering effective breast cancer risk counseling to African American women. 相似文献
78.
A Shuper M Mukamel M Mimouni M Lerman I Varsano 《Archives of disease in childhood》1983,58(9):745-747
Psychogenic cough is croupy and explosive, never occurs during sleep, and is not affected by antitussive drugs. Physical and radiographic examinations of the respiratory tract and microbiological investigations are normal. Bronchial asthma manifested as chronic cough should be excluded in each patient by lung function testing. 相似文献
79.
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