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421.
The effect of conventional treatment on insulin action in subcutaneous adipose tissue was studied in 6 patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of the hormone on glucose oxidation were determined before and after 6-14 months of treatment with diet plus sulphonylurea. Glycaemic control and in vivo insulin sensitivity were significantly improved by the treatment. Before treatment, the adipocyte insulin receptor binding and the sensitivity to insulin stimulation of adipose tissue glucose oxidation were normal and did not change after treatment. In contrast, the maximum insulin-induced glucose oxidation was markedly decreased before treatment, whereas it was totally normalized after treatment. The conclusion is that insulin resistance in adipose tissue of NIDDM subjects is solely due to post-receptor defects in insulin action. This resistance is completely off-set by conventional treatment with diet plus sulphonylurea. 相似文献
422.
Relationship between beta-2 adrenoceptor gene haplotypes and adipocyte lipolysis in women 总被引:2,自引:0,他引:2
Eriksson P Dahlman I Rydén M Hoffstedt J Arner P 《International journal of obesity (2005)》2004,28(2):185-190
BACKGROUND AND AIMS: The beta(2)-adrenergic receptors are important for adipocyte lipolysis regulation by catecholamines in humans. The beta(2)-adrenoceptor gene is highly polymorphic. The role of these genetic variations for adipocyte lipolysis was investigated. DESIGN AND METHODS: Six single-nucleotide polymorphisms (SNPs) in the promotor region and four SNPs in the coding region (leading to amino-acid substitution) of the beta(2)-adrenoceptor gene were determined in 141 overweight or obese, but otherwise healthy women. Lipolysis experiments were performed on isolated subcutaneous adipocytes. RESULTS: Three homozygous haplotypes (6/6, 4/4 and 2/2) were found that differed about 500-fold in noradrenaline sensitivity or beta(2)-adrenoceptor sensitivity (6/6>2/2>4/4, P=0.01). The haplotypes also differed by 100% in maximum noradrenaline-induced lipolysis rates (6/6>2/2>4/4). However, there was no influence on beta(1)-, beta(3)- or alpha(2)A-adrenoceptor sensitivity. Heterozygosity at one or several SNPs in the haplotypes influenced the beta(2)-adrenoceptor sensitivity significantly. CONCLUSION: Multiple SNPs in the beta(2)-adrenoceptor gene form several haplotypes that markedly influence beta(2)-receptor function- and catecholamine-induced lipolysis in fat cells. These haplotypes may be important genetic factors behind impaired lipolysis in obesity. 相似文献
423.
Modulation of interleukin-1-induced alterations in cartilage proteoglycan metabolism by activation of protein kinase C 总被引:2,自引:0,他引:2
Interleukin-1 (IL-1) stimulates proteoglycan degradation and prostaglandin E2 (PGE2) release and inhibits proteoglycan synthesis by cartilage in organ culture. Addition of the protein kinase C (PKC) activator, mezerein, resulted in the concentration-dependent inhibition of IL-1 activity on proteoglycan metabolism. Similar effects were seen with other compounds which stimulated PKC, such as teleocidin B4 and phorbol dibutyrate (PDBu), but not with a phorbol analog that is inactive in stimulating PKC. Simultaneous addition of the PKC antagonist, staurosporine, blocked the mezerein-induced inhibition of IL-1 activity on both proteoglycan degradation and synthesis in a concentration-related manner. In contrast to its inhibition of the effect of IL-1 on proteoglycan metabolism, mezerein did not block the release of PGE2 by cartilage in response to IL-1 but caused a synergistic stimulation of PGE2 release. Importantly, in cultures made deficient in PKC by prolonged incubation with PDBu, the effects of this PKC agonist on proteoglycan breakdown and PGE2 were blocked, while stimulation by IL-1 persisted. These data indicate that the effects of IL-1 on proteoglycan metabolism and prostaglandin production are mediated by an intracellular signal distinct from PKC and suggest that activation of PKC in chondrocytes may play a role in modulating the action of IL-1 on proteoglycan metabolism. 相似文献
424.
Adrenergic regulation of lipolysis in human adipocytes: findings in hyper- and hypothyroidism 总被引:3,自引:0,他引:3
H Wahrenberg P Engfeldt P Arner A Wennlund J Ostman 《The Journal of clinical endocrinology and metabolism》1986,63(3):631-638
In isolated sc adipocytes removed from hyperthyroid patients, the specific binding of [3H]dihydroalprenolol and [125I]iodocyanopindolol was greater than that in adipocytes from normal subjects. Based on Scatchard analysis of the [125I] iodocyanopindolol data, this difference was due to a significant (P less than 0.01) increase in adrenoceptor number, which was 1.72 +/- 0.18 (+/- SEM) pmol/10(7) cells in the hyperthyroid patients and 0.94 +/- 0.16 pmol/10(7) cells in the normal subjects. When the patients were restudied when they were euthyroid, a significant decrease in the specific binding of the two radioligands was found. In hyperthyroidism, the lipolytic responsiveness (maximum effect) to norepinephrine was increased 5-fold, and that to isopropylnorepinephrine was increased 2-fold. No changes in either the binding of [3H]yohimbine or the antilipolytic effect of clonidine were found. In isolated adipocytes from hypothyroid patients, the specific binding of [3H]dihydroalprenolol and [125I]iodocyanopindolol did not differ from that in the normal subjects. The basal rate of lipolysis (P less than 0.025) and the lipolytic responsiveness to isopropylnorepinephrine (P less than 0.025) were significantly lower than normal, and the response to norepinephrine was almost completely abolished in the hypothyroid state. The sensitivity and responsiveness to clonidine were comparable in the adipocytes of the hypothyroid patients and normal subjects. There was no difference between hypothyroid patients and normal subjects in the binding of [3H]yohimbine. We conclude that the sc adipocytes in hyperthyroidism have beta-adrenergic, but not alpha 2-adrenergic abnormalities. Although there was a moderate increase in the beta-adrenoceptor density in hyperthyroidism, the most important abnormality, namely the increased responsiveness to the catecholamines, seems to be located beyond the receptor level. On the other hand, in hypothyroidism, there was no evidence of changes in either the alpha 2- or the beta-adrenoceptors. The chief abnormality in hypothyroidism, decreased responsiveness to beta-adrenergic agonists, also would appear to be localized beyond the adrenoceptor level. 相似文献
425.
A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects 总被引:7,自引:0,他引:7
Dahlman I Kaaman M Olsson T Tan GD Bickerton AS Wåhlén K Andersson J Nordström EA Blomqvist L Sjögren A Forsgren M Attersand A Arner P 《The Journal of clinical endocrinology and metabolism》2005,90(10):5834-5840
CONTEXT: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. OBJECTIVES: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. DESIGN: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human s.c. adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. RESULTS: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. CONCLUSIONS: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance. 相似文献
426.
The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity 总被引:8,自引:2,他引:8
Aims/hypothesis. Plasminogen activator inhibitor 1 (PAI-1) increases in several insulin-resistant conditions such as obesity. We tested the
hypothesis that the PAI-1 gene might be a candidate for obesity and Type II (non-insulin-dependent) diabetes mellitus. Methods. We investigated the frequency of a common and functional –675 4G/5G promoter polymorphism in the PAI-1 gene in 188 lean, 70 overweight (BMI 25–30 kg/m2) and 247 obese otherwise healthy Scandinavian subjects. Results. The genotypic (p = 0.002), or allelic (p = 0.0004) distribution differed markedly between the three groups. Homozygocity for 4G was more common among obese people, whereas homozygocity for 5G was more common among lean subjects. Heterozygocity was evenly distributed. The lean and overweight groups did not differ
in frequency distribution. The relative risk for being obese in comparison to being lean for 4G/4G was threefold higher (p = 0.0003). Also, carriers of the 4G allele in the heterozygous or homozygous form were distributed differently between the three groups (p = 0.006). The 4G carriers were more common among the obese than the lean group. The latter group did not differ from the overweight group.
The relative risk of being obese in comparison with lean was twofold increased in 4G carriers (p = 0.0015). Similar results were obtained in men and women. Conclusion/interpretation. Thus, the common –675 4G/5G polymorphism in the PAI-1 gene is strongly linked to obesity and a markedly increased risk for obesity is associated with the 4G allele in its homozygous form. [Diabetologia (2002) 45: ▪–▪]
Received: 27 August 2001 and in revised form: 1 October 2001 相似文献
427.
428.
429.
Linden T. Hu Manuel A. Eskildsen Catherine Masgala Allen C. Steere Elizabeth C. Arner Michael A. Pratta Alan J. Grodzinsky Andrew Loening George Perides 《Arthritis \u0026amp; Rheumatology》2001,44(6):1401-1410