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Background
Growing discontent with the k-level system for functional classification of patients with limb loss and movement of healthcare toward evidence-based practice has resulted in the need for alternative forms of functional classification and development of clinical practice guidelines to improve access to quality prosthetic interventions. The purpose of this project was to develop and present a clinical practice recommendation for exercise testing in prosthetic patient care based on the results and synthesis of a systematic literature review.Methods
Database searches of PubMed, Google Scholar, Web of Science, and Cochrane were conducted and articles reviewed. Of the potential 1386 articles 10 met the criteria for inclusion. These articles were assessed using the critical appraisal tool of the United Kingdom National Service Framework for Long-Term Conditions. Of the 10 included articles eight were of high, one of medium, and one of low, quality. Data from these articles were synthesized into 6 empirical evidence statements, all qualifying for research grade A. These statements were used to develop the proposed clinical practice guideline.Results
While the results of this systematic review were not able to support the direct connection between cardiorespiratory performance and K-levels, the literature did support the ability of exercise testing results to predict successful prosthetic ambulation in some demographics. Both continuous maximum-intensity single lower extremity ergometer propelled by a sound limb and intermittent submaximal upper extremity ergometer protocols were found to be viable evaluation tools of cardiorespiratory fitness and function in the target population.Conclusion
The ability to sustain an exercise intensity of ≥50% of a predicted VO2max value in single leg cycle ergometry testing and achievement of a sustained workload of 30 W in upper extremity ergometry testing were found to be the strongest correlates to successful ambulation with a prosthesis. VO2 values were found to increase in amputee subjects following a 6-week exercise program. These synthesized results of the systematic literature review regarding exercise testing in patients with loss of a lower extremity were used to develop and a present a clinical treatment pathway.Purpose
The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.Methods
We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.Results
Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT.Conclusions
Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.
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