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1.
Changes in anal pressure have been monitored during the induction of anaesthesia. Falls in pressure accompany loss of consciousness following bolus doses of commonly used intravenous and inhalational anaesthetic agents. Subsequent rises in pressure towards pre-anaesthetic levels are usually associated with the time taken to correct responses and initial recovery. Premedication, including anticholinergic drugs in conventional dosage, does not affect anal pressure.  相似文献   
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Patients with hepatic metastases from colorectal cancer appear to be resistant to most forms of therapy. Recent reports suggest synergism between systemically administered recombinant interleukin-2 (rIL-2) and 5-fluorouracil (5-FU) with responses documented in the treatment of advanced colonic tumours albeit with significant toxicity. Local continuous infusion of rIL-2 into selected sites may reduce toxicity and increase efficacy. We have assessed the feasibility of continuously infusing rIL-2 into the region of a hepatic metastasis in 3 patients via a catheter placed within the liver under ultrasound guidance in a regimen including systemic rIL-2 and 5FU.  相似文献   
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Purpose

The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice.

Methods

The RESPOND (Effectiveness of DMF and Its Impact on PROs in Suboptimal GA Responders With RMS) study was a Phase IV, prospective, multicenter, open-label, single-arm, 12-month observational trial. The study was conducted in the United States at 63 sites between August 2013 and February 2016. Patients diagnosed with RMS who experienced a suboptimal response to GA (defined as perceived suboptimal efficacy, intolerance, or poor adherence to GA) were eligible for enrollment. DMF treatment was initiated within 60 days of enrollment. The primary objective was to estimate the annualized relapse rate (ARR) at 12 months based on data collected from medical records and compare it with the 12 months before DMF initiation. Secondary objectives of the study included assessing the change in PRO scores from baseline to 12 months; PROs were recorded before and at 6 and 12 months after DMF initiation.

Findings

Of the 318 patients included in the analysis population, 247 (78%) completed treatment. Mean (SD) time on GA treatment before switching to DMF was 51.3 months (49.1 months). The ARR (95% CI) reported for the 12 months before DMF initiation was 0.49 (0.42–0.57) compared with 0.11 (0.07–0.17) at 12 months after DMF initiation, representing a 78% reduction in ARR (P < 0.0001). Statistically significant improvements from baseline were observed for multiple PROs, including the 36-item Short Form Health Survey physical and mental component summaries (P = 0.0201 and P = 0.0014, respectively), the 5-item Modified Fatigue Impact Scale (P = 0.0002), the 14-item Treatment Satisfaction Questionnaire for Medication (P < 0.0001), and the 7-item Beck Depression Inventory (P = 0.0117).

Implications

DMF may be an effective treatment option in patients with RMS who experience a suboptimal response to GA. The results should be interpreted with caution due to the observational nature of the study and the lack of a control group. Other limitations of the study include a potential bias due to regression to the mean and lack of randomization. ClinicalTrials.gov identifier: NCT01903291.  相似文献   
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A review of 26 tuberculosis outbreaks in the United States (2002–2011) showed that initial source case-patients had long infectious periods (median 10 months) and were characterized by substance abuse, incarceration, and homelessness. Improved timeliness of diagnosis and thorough contact investigations for such cases may reduce the risk for outbreaks.  相似文献   
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There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease. Baseline control serum (n=66) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by proton nuclear magnetic resonance ((1)H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm amino acid changes detected by (1)H NMR. Data were correlated with body composition, emphysema and systemic inflammation. (1)H NMR identified decreased lipoproteins, N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched-chain amino acids (BCAAs) observed in GOLD stage IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies, and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also displayed decreased serum creatine, glycine and N,N-dimethylglycine. LC-MS/MS confirmed (1)H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage IV patients. NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.  相似文献   
7.
The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of schizophrenia‐related behavior in the rat. Our previous report demonstrated that cerebrolysin (Cbl), a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair, promoted recovery of dendritic and neuronal damage of the prefrontal cortex and nucleus accumbens and behavioral improvements in postpubertal nVHL rats. We recently demonstrated that nVHL animals exhibit dendritic atrophy and spine loss in the basolateral amygdala (BLA). This study aimed to determine whether Cbl treatment was capable of reducing BLA neuronal alterations observed in nVHL rats. The morphological evaluation included examination of dendrites using the Golgi‐Cox procedure and stereology to quantify the total cell number in BLA. Golgi‐Cox staining revealed that nVHL induced dendritic retraction and spine loss in BLA pyramidal neurons. Stereological analysis demonstrated nVHL also produced a reduction in cells in BLA. Interestingly, repeated Cbl treatment ameliorated dendritic pathology and neuronal loss in the BLA of the nVHL rats. Our data show that Cbl may foster recovery of BLA damage in postpubertal nVHL rats and suggests that the use of neurotrophic agents for the management of some schizophrenia‐related symptoms may present an alternative therapeutic pathway in these disorders. Synapse, 68:31–38, 2014 . © 2013 Wiley Periodicals, Inc.  相似文献   
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Eleven patients suffering from intra-abdominal malignancy were treated with various doses of intraperitoneal mitomycin C adsorbed onto activated carbon particles. Seven of the patients underwent resection of their primary gastric tumour and all developed potentially life-threatening severe complications that proved to be fatal in four patients. The pattern of complications seen in these patients was unusual in patients undergoing gastrectomy and must be presumed to be secondary to the intraperitoneal mitomycin C. Intraperitoneal mitomycin C at a dose of 25 mg and 50 mg in the presence of an anastomosis or other suture line does not appear to be safe.  相似文献   
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