全文获取类型
收费全文 | 167篇 |
免费 | 13篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 13篇 |
妇产科学 | 6篇 |
基础医学 | 16篇 |
口腔科学 | 3篇 |
临床医学 | 19篇 |
内科学 | 52篇 |
皮肤病学 | 5篇 |
神经病学 | 5篇 |
特种医学 | 16篇 |
外科学 | 11篇 |
综合类 | 6篇 |
预防医学 | 6篇 |
眼科学 | 4篇 |
药学 | 13篇 |
肿瘤学 | 8篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 3篇 |
2014年 | 1篇 |
2013年 | 4篇 |
2012年 | 7篇 |
2011年 | 13篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 3篇 |
2007年 | 9篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 11篇 |
1997年 | 11篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有185条查询结果,搜索用时 15 毫秒
1.
2.
Alan Ma Sunita Gurnasinghani Edwin P. Kirk Conor McClenaghan Gautam K. Singh Dorothy K. Grange Chetan Pandit Yung Zhu Tony Roscioli George Elakis Michael Buckley Bhavesh Mehta Philip Roberts Jonathan Mervis Andrew Biggin Colin G. Nichols 《American journal of medical genetics. Part A》2019,179(8):1585-1590
Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of KATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg–1 kg–1 day–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg?1 kg?1day?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS. 相似文献
3.
4.
5.
Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium 总被引:12,自引:0,他引:12
van Hinsbergh VW; Bertina RM; van Wijngaarden A; van Tilburg NH; Emeis JJ; Haverkate F 《Blood》1985,65(2):444-451
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. 相似文献
6.
7.
Brennan L Shine A Hewage C Malthouse JP Brindle KM McClenaghan N Flatt PR Newsholme P 《Diabetes》2002,51(6):1714-1721
Early experiments indicated that islet beta-cells substantially metabolized L-alanine but that insulin secretion was largely unaffected by the amino acid. It was subsequently demonstrated using more intricate studies that L-alanine is a strong stimulus to insulin secretion in the presence of glucose in normal rodent islets and beta-cell lines. Using (13)C nuclear magnetic resonance (NMR), we have demonstrated substantial oxidative metabolism of L-alanine by the clonal beta-cell line BRIN-BD11, with time-dependent increases in production of cellular glutamate and aspartate. Stimulatory effects of L-alanine on insulin secretion were attenuated by the inhibition of beta-cell oxidative phosphorylation using oligomycin. Additionally, we detected substantial production of lactate, alanine, and glutamate from glucose (16.7 mmol/l) after 60 min. On addition of 10 mmol/l L-alanine to a stimulus of 16.7 mmol/l glucose, the utilization rate of glucose increased approximately 2.4-fold. L-Alanine dramatically enhanced NMR-measurable aspects of glucose metabolism (both oxidative and nonoxidative). The enhanced rate of entry of glucose-derived pyruvate into the tricarboxylic acid (TCA) cycle in the presence of alanine may have stimulated rates of generation of key metabolites, including ATP, which affect the insulin secretory process. Thus L-alanine metabolism, in addition to the enhancing effect on glucose metabolism, contributes to the stimulatory effects of this amino acid on insulin secretion in vitro. 相似文献
8.
The JB6 mouse epidermal cell system has been used extensively as an in
vitro transformation model for the study of tumor promotion. The standard
JB6 cell assay for promotion of transformation is carried out in soft agar
or other anchorage independent conditions. The present study was directed
to the development of an in vivo model to distinguish the promotion
resistant (P-) and promotion sensitive (P+) progression phenotypes. Results
indicate that the grafting assay distinguishes P- and P+ cells in vivo with
P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant
negative mutant jun TAM67 blocks both anchorage independent transformation
response and graft bed tumor formation by P+ cells, suggesting that the
requirement for AP-1 activation in transformation now applies in vivo.
Expression of mutated p53 produced a gain of P+ phenotype in P- cells in
vitro, but not in vivo. Histochemical and Northern blot analysis for
expression of various keratinocyte markers revealed no evidence for
expression, suggesting a loss of keratinocyte markers following
establishment in culture. In summary, the skin-grafting assay described in
this study appears to be a valid in vivo assay for distinguishing the
preneoplastic progression phenotypes represented by JB6 P- and P+ cells.
相似文献
9.
The B vitamin nicotinamide (NIC), commonly known as niacin, is currently in trial as a potential means of preventing Type 1 diabetes in first-degree relatives of affected individuals. Sodium butyrate (BUT) a common dietary micronutrient has also been reported to have beneficial effects on the differentiation and function of pancreatic beta cells. Cultured rat insulin-secreting BRIN-BD11 cells were used to investigate the effects of 3 days exposure to NIC (10 mM) and BUT (1 mM) both alone and in combination on beta cell function. Culture with NIC and/or BUT resulted in reduction of growth, insulin content and basal insulin secretion. BUT additionally decreased cell viability whilst NIC had no significant effect. Treatment with either agent abolished beta cell glucose sensitivity but insulin secretory responsiveness to a wide range of beta cell stimulators, including a depolarizing concentration of K+, elevation of Ca2+ and activation of adenylate cyclase and protein kinase C, were enhanced. These data illustrate that long term exposure to NIC and BUT has both positive and negative effects on the function of insulin-secreting cells. 相似文献
10.
Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1, 1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100 - 400 microM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8. 4 mM) glucose. Long-term exposure (3 - 18 h) to 100 microM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 microM BTS 67 582 or 200 microM tolbutamide at 12 - 18 h (P<0.001). Similarly 3 - 18 h culture with the sulphonylurea, tolbutamide (100 microM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 microM BTS 67 582 or 100 microM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 microM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 microM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents. 相似文献