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111.
BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research. 相似文献
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Brandon DL. Marshall Evan Wood Jean A. Shoveller Jane A. Buxton Julio SG. Montaner Thomas Kerr 《Prevention science》2011,12(2):173-180
The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort
of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June
2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study’s commencement were
eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. The
outcome was time to first report of methamphetamine injection. Time-updated independent variables of interest included sociodemographic
characteristics, drug use patterns, and social, economic and environmental factors. Of 1317 eligible individuals, the median
age was 39.9 and 522 (39.6%) were female. At the study’s conclusion, 200 (15.2%) participants had initiated injecting methamphetamine
(incidence density: 4.3 per 100 person-years). In multivariate analysis, age (adjusted hazard ratio [aHR]: 0.96 per year older,
95%CI: 0.95–0.98), female sex (aHR: 0.58, 95%CI: 0.41–0.82), sexual abuse (aHR: 1.63, 95%CI: 1.18–2.23), using drugs in Vancouver’s
drug scene epicentre (aHR: 2.15 95%CI: 1.49–3.10), homelessness (aHR: 1.43, 95%CI: 1.01–2.04), non-injection crack cocaine
use (aHR: 2.06, 95%CI: 1.36–3.14), and non-injection methamphetamine use (aHR: 3.69, 95%CI: 2.03–6.70) were associated with
initiating methamphetamine injection. We observed a high incidence of methamphetamine initiation, particularly among young
IDU, stimulant users, homeless individuals, and those involved in the city’s open drug scene. These data should be useful
for the development of a broad set of interventions aimed at reducing initiation into methamphetamine injection among IDU. 相似文献
114.
Robert P. Carlyon John M. Deeks François Guérit Wiebke Lamping Alexander J. Billig Charles H. Large Shakeel R. Saeed Peter Harris 《Journal of the Association for Research in Otolaryngology》2018,19(6):669-680
Temporal processing by cochlear implant listeners is degraded and is affected by auditory deprivation. The fast-acting Kv3.1 potassium channel is important for sustained temporally accurate firing and is also susceptible to deprivation, the effects of which can be partially restored in animals by the molecule AUT00063. We report the results of a randomised placebo-controlled double-blind study on psychophysical tests of the effects of AUT00063 on temporal processing by CI listeners. The study measured the upper limit of temporal pitch, gap detection, and discrimination of low rates (centred on 120 pps) for monopolar pulse trains presented to an apical electrode. The upper limit was measured using the optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds were obtained for the other two measures using an adaptive procedure. Twelve CI users (MedEl and Cochlear) were tested before and after two periods of AUT00063 or placebo in a within-subject crossover study. No significant differences occurred between post-drug and post-placebo conditions. This absence of effect occurred despite high test-retest reliability for all three measures, obtained by comparing performance on the two baseline visits, and despite the demonstrated sensitivity of the measures to modest changes in temporal processing obtained in other studies from our laboratory. Hence, we have no evidence that AUT00063 improves temporal processing for the doses and patient population employed. 相似文献
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DL Domingo MI Trujillo SE Council MA Merideth LB Gordon T Wu WJ Introne WA Gahl TC Hart 《Oral diseases》2009,15(3):187-195
Objective: Hutchinson-Gilford progeria syndrome (HGPS) is a rare early-onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene ( LMNA ) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include 'bird-like' facies, alopecia, craniofacial disproportion, and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS.
Methods: Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified.
Results: Radiographic findings included hypodontia ( n = 7), dysmorphic teeth ( n = 5), steep mandibular angles ( n = 11), and thin basal bone ( n = 11). Soft tissue findings included ogival palatal arch ( n = 8), median sagittal palatal fissure ( n = 7), and ankyloglossia ( n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) ( P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.
Conclusion: Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS. 相似文献
Methods: Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified.
Results: Radiographic findings included hypodontia ( n = 7), dysmorphic teeth ( n = 5), steep mandibular angles ( n = 11), and thin basal bone ( n = 11). Soft tissue findings included ogival palatal arch ( n = 8), median sagittal palatal fissure ( n = 7), and ankyloglossia ( n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) ( P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.
Conclusion: Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS. 相似文献
119.
John Patrick Browne Jan H. van der Meulen James D. Lewsey Donna L. Lamping Nick Black 《Journal of clinical epidemiology》2010,63(8):865-874
ObjectiveTo generate anchor-based values for the “minimally important difference” (MID) for a number of commonly used patient-reported outcome (PRO) measures and to examine whether these values could be applied across the continuum of preoperative patient severity.Study Design and SettingSix prospective cohort studies of patients undergoing elective surgery at hospitals in England and Wales. Patients completed questionnaires about their health and health-related quality of life before and after surgery. MID values were calculated using the mean change score for a reference group of patients who reported they were “a little better” after surgery minus the mean change score for those who said they were “about the same.” Pearson's correlation was used to examine the association between baseline severity and change scores in the reference group. Baseline severity was expressed in two ways: first in terms of preoperative scores and second in terms of the average of pre- and postoperative scores (Oldham's method).ResultsOf the 10 PRO measures examined, eight demonstrated a moderate or high positive association between preoperative scores and MID values. Only two measures demonstrated such an association when Oldham's measure of baseline severity was used.ConclusionIn general, there is little association between baseline severity and MID values. However, a moderate association persists for some measures, and it is recommended that researchers continue to test for this relationship when generating anchor-based MID values from change scores. 相似文献
120.
Christopher R Heery Geraldine OSullivan-Coyne Ravi A Madan Lisa Cordes Arun Rajan Myrna Rauckhorst Elizabeth Lamping Israel Oyelakin Jennifer L Marté Lauren M Lepone Renee N Donahue Italia Grenga Jean-Marie Cuillerot Berend Neuteboom Anja von Heydebreck Kevin Chin Jeffrey Schlom James L Gulley 《The lancet oncology》2017,18(5):587-598