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1.
Serum insulin and leptin levels in valproate-associated obesity   总被引:4,自引:4,他引:14  
PURPOSE: Weight gain is an important adverse effect of valproate (VPA) therapy, and it is associated with hyperinsulinemia and hyperandrogenism in women with epilepsy. Leptin is considered a signaling factor regulating body weight and energy metabolism. In human subjects, obesity is in general associated with elevated serum leptin levels, suggesting decreased sensitivity to leptin. The present study aimed at evaluating the role of insulin and leptin in VPA-related obesity. METHODS: Body mass index (BMI) was calculated, and serum insulin and leptin levels were measured in 81 patients with epilepsy taking VPA and in 51 healthy control subjects. RESULTS: Forty (49%) of the patients taking VPA and 25 (49%) of the control subjects were obese. The mean insulin levels were higher in VPA-treated patients than in the control subjects despite similar BMI values, when all subjects were included in the comparison. Both obese male and female patients taking VPA had higher serum insulin levels than the respective control subjects with similar BMI values. Serum insulin levels also were higher in lean male and lean female patients compared with the lean control subjects of same sex. Serum leptin levels did not differ between the VPA-treated patients and the control subjects. CONCLUSIONS: Both obese and lean patients taking VPA for epilepsy have hyperinsulinemia, suggesting development of insulin resistance. This may be one of the factors leading to weight gain during VPA treatment. However, the results of the present study do not suggest an independent role for leptin in the pathogenesis of VPA-related obesity.  相似文献
2.
OBJECTIVE: Among antipsychotics, clozapine ranks highest in terms of the risk for weight gain and developing diabetes. However, the mechanism by which clozapine induces weight gain and diabetes remains unclear. The aim of this study was to determine the mechanism of clozapine-induced weight gain and hyperglycemia, and to clarify whether clozapine-induced hyperglycemia results from impairment of the system regulating appetite. METHODS: Circulatory glucose, insulin, leptin and ghrelin levels were analyzed after acute administration of clozapine in rats. Clozapine (10 mg/kg) or a vehicle was injected intraperitoneally and blood samples were collected at 0, 15, 30, and 60 min after the injection. Clozapine (5, 10 or 20 mg/kg) or the vehicle was given, and blood samples were collected at 30 min after the injection. Since clozapine has receptor affinity for multiple neurotransmitters, selective antagonists of it, including dopamine, serotonin, alpha-adrenergic, muscarine and histamine were administered to clarify the pathway of clozapine-induced blood glucose and changes in plasma ghrelin. RESULTS: Clozapine administration increased the blood glucose level at all time points (p<0.05) compared to controls. Plasma ghrelin was elevated at 30 min (p=0.0124) and 60 min (p=0.00152). Blood glucose was increased in rats given 5 (p=0.0344), 10 (p<0.0001), or 20 mg/kg (p<0.0001) clozapine, while plasma ghrelin was increased in rats treated with 10 mg/kg (p=0.0009) or 20 mg/kg (p=0.0059) clozapine. Blood glucose was increased in rats treated with a selective alpha1-adrenergic receptor antagonist (p<0.0001), while plasma ghrelin was significantly increased in rats given a selective alpha1- (p=0.025) or alpha2-adrenergic receptor antagonist (p=0.0003). CONCLUSIONS: Clozapine impairs glucose metabolism and the appetite-regulation system. Clozapine increases blood glucose independent of insulin. The antagonistic action of alpha-adrenergic receptors is one of the mechanisms that induces both hyperglycemia and elevation of ghrelin.  相似文献
3.
Obesity and mental disorders in the adult general population   总被引:3,自引:0,他引:3  
OBJECTIVE: The aim of this study was to investigate (i) the associations between mental disorders (in particular the anxiety disorders) and obesity in the general population and (ii) potential moderators of those associations (ethnicity, age, sex, and education). METHODS: A nationally representative face-to-face household survey was conducted in New Zealand with 12,992 participants 16 years and older, achieving a response rate of 73.3%. Ethnic subgroups (Maori and Pacific peoples) were oversampled. Mental disorders were measured with the Composite International Diagnostic Interview (CIDI 3.0). Height and weight were self-reported. Obesity was defined as a body mass index (BMI) of 30 kg/m(2) or greater. RESULTS: Obesity was significantly associated with any mood disorder (OR 1.23), major depressive disorder (OR 1.27), any anxiety disorder (OR 1.46), and most strongly with some individual anxiety disorders such as post-traumatic stress disorder (PTSD) (OR 2.64). Sociodemographic correlates moderated the association between obesity and mood disorders but were less influential in obesity-anxiety disorder associations. Adjustment for the comorbidity between anxiety and mood disorders made little difference to the relationship between obesity and anxiety disorders (OR 1.36) but rendered the association between obesity and mood disorders insignificant (OR 1.05). CONCLUSION: Stronger associations were observed between anxiety disorders and obesity than between mood disorders and obesity; the association between PTSD and obesity is a novel finding. These findings are interpreted in light of research on the role of anxiety in eating pathology, and deserve the further attention of researchers and clinicians.  相似文献
4.
5.
The goal of the study was to elucidate the relationship between serum circulating brain-derived neurotrophic factor (BDNF) and body weight reduction via lifestyle modification and behavior therapy in obese non-diabetic patients with chronic schizophrenia. Thirty-three obese non-diabetic subjects with schizophrenia treated with stable antipsychotic medication in a day-care unit for at least 3 months were recruited. Thirty age-, body weight-matched subjects without psychiatric disorders were enrolled as controls. All participants underwent a 10-week weight reduction program, including lifestyle modification, psychosocial treatment, behavior therapy and exercise in the day-care unit. Blood biochemistry, serum BDNF, adipokine (adiponectin), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha and interleukin-6) and oral glucose tolerance test were evaluated before and after the program. Serum BDNF concentrations were significantly lower among patients with schizophrenia compared to control subjects. Serum BDNF levels were significantly increased following the weight reduction program. Elevations in serum BDNF levels were positively correlated with body weight and body mass index reduction. Altogether, our results demonstrate that a non-pharmacological weight reduction program effectively reduces body weight with significant elevation of serum BDNF levels in obese non-diabetic patients with schizophrenia.  相似文献
6.
Endocrine effects of valproate in adolescent girls with epilepsy   总被引:1,自引:0,他引:1  
Summary:  Purpose: To investigate the effect of epilepsy and/or valproate (VPA) monotherapy on physical growth, weight gain, pubertal development, and hormonal status in adolescent girls with epilepsy.
Methods: The study group included 88 consecutive female patients with epilepsy aged 6–20 years (28 premenarche, 60 postmenarche) attending an endocrinology institute of a major tertiary center. Forty-five patients were under treatment with VPA, and 43 were before treatment initiation. The groups were compared for the relevant biochemical, anthropometric, ultrasonographic, and endocrine parameters.
Results: No statistically significant differences were found in any of the parameters studied between the groups, as a whole or by menarche status. The treated postmenarcheal subgroup had a higher mean testosterone level than the untreated postmenarcheal controls (1.83 ± 0.65 vs. 0.88 ± 0.24, p = 0.006). Body mass index–standard deviation score (BMI-SDS) was 0.75 in the treated group and 0.63 in the untreated group; rates of obesity were 16.3% and 15.5%, respectively. No between-group differences were found in menses irregularities, hirsutism, or acne. No correlation was found between duration or dosage of treatment and BMI-SDS, height–SDS, or androgen level. The treated group had higher levels of thyroid-stimulating hormone and lower levels of free thyroxine than did the untreated group, although still within normal range.
Conclusions: Long-term treatment with VPA in girls with epilepsy is associated with increased testosterone levels after menarche, without clinical hyperandrogenism, polycystic ovary syndrome, or an increase in BMI-SDS. VPA is a good treatment option in this age group but should be accompanied by careful endocrine observation.  相似文献
7.
INTRODUCTION: Generation of platelet-derived microparticle (PMP) is implicated in cardiovascular disease (CVD). However, the influence of adiposity and weight reduction on PMP generation remains to be fully elucidated. We compared PMP generation and fibrinolytic parameters between 49 non-diabetic obese (obese group) and 37 age-matched non-obese subjects (control group), and compared the effects of weight reduction on the parameters between a 12-week calorie restricted diet and diet with aerobic exercise in obese subjects. MATERIALS AND METHODS: PMP, plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) antigen were measured before and after intervention. RESULTS: Before intervention, PMP, PAI-1 activity and t-PA antigen values were elevated in the obese group compared with the control group. In all 86 subjects of both groups, these three parameters correlated with body mass index, waist circumference and fat tissue mass. There was a positive correlation between plasma levels of fibrinolytic parameters and visceral fat area (VFA). PMP values correlated with subcutaneous fat area (SFA). The intervention significantly reduced PMP, PAI-1 activity and t-PA antigen levels. There was a significant correlation between percentages of changes in PMP values and those in BMI, fat tissue mass and VFA in the obese group. No additional effect of exercise on PMP or fibrinolytic parameters was observed. CONCLUSIONS: Overproduction of PMP and fibrinolytic abnormalities may be associated with excessive adipose tissue. Weight reduction by either calorie restriction with or without exercise improves fibrinolytic abnormalities and PMP overproduction, probably through reduction of adipose tissue.  相似文献
8.
When pituitaries are intact, hypothalamic knife cuts produce obesity in adult rats but not in weanlings. Knife cut weanling females do not usually begin to become obese until after they are 7 weeks old. When pituitaries are removed, symmetrical or asymmetrical knife cuts produce obesity promptly in both adults and weanlings. Obesity indices that correct for stunted linear growth reveal that in adults the degree of obesity is independent of the presence or absence of the pituitary. Based on these findings we speculate that there may be two appetite regulating systems, a juvenile one involving the pituitary, and an adult one involving the hypothalamus.  相似文献
9.
A translation defect in the messenger RNA that translates the glycosylated protein pro-opiocortin may account for many of the endocrine and behavioral problems in the C57BL/6J ob/ob genetically obese mouse. This is the first proposal of a mechanism for the generation, by a single gene, of the complete set of abnormal behaviors and endocrine disturbances in the obese mouse.  相似文献
10.
By employing neutron activation analysis, endogenous content of gold was estimated quantitatively in discrete brain areas and in subcellular fractions of the hypothalamus of gold thioglucose (GTG) induced obese mice. The highest concentration of gold was obtained in the ventromedial hypothalamus (VMH) reaching approximately 100 ng/mg wet tissue. Significantly higher concentrations were observed in other hypothalamic subareas followed by certain limbic areas and the thalamus, while in the cerebral and the cerebellar cortex the gold concentration was very low. Subcellularly, the hypothalamic gold was principally recovered in the supernatant fraction particularly after a hyposmotic shock treatment of the crude mitochondrial fraction. Contrary to GTG, treatment with gold thiomalate (GTM) did not induce obesity in the mouse, although considerable amount of gold was observed in the VMH, a finding suggesting the existence in the VMH of at least a two step mechanisms for inducing GTG obesity. To identify the satiety neuron transmitter, an analysis of certain enzyme activities involved in the synthesis of known transmitters, such as acetylcholine or γ-aminobutyric acid (GABA), was made in the GTG-obese mice. There were no significant changes in any of the areas functionally related to the VMH.  相似文献
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