全文获取类型
收费全文 | 253篇 |
免费 | 27篇 |
国内免费 | 3篇 |
专业分类
儿科学 | 22篇 |
妇产科学 | 2篇 |
基础医学 | 36篇 |
临床医学 | 20篇 |
内科学 | 46篇 |
皮肤病学 | 1篇 |
神经病学 | 43篇 |
特种医学 | 6篇 |
外科学 | 43篇 |
综合类 | 1篇 |
预防医学 | 26篇 |
药学 | 18篇 |
肿瘤学 | 19篇 |
出版年
2023年 | 6篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 10篇 |
2019年 | 13篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 10篇 |
2015年 | 8篇 |
2014年 | 19篇 |
2013年 | 19篇 |
2012年 | 31篇 |
2011年 | 27篇 |
2010年 | 15篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 11篇 |
2006年 | 18篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 7篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
排序方式: 共有283条查询结果,搜索用时 31 毫秒
1.
Stijnen Annemiek M. Hovinga Suzanne Langemeijer Mariska W. E. Hoogerkamp Arendien van Bezooijen Cornells F. A. Danhof Meindert 《Pharmaceutical research》1993,10(7):1046-1051
The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991. 相似文献
2.
High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease 总被引:8,自引:0,他引:8
An increase in bile ductular structures is observed in diverse human liver diseases. These structures harbour the progenitor cell compartment of the liver. Since ATP-binding cassette (ABC) transporters may have a cytoprotective role in liver disease, an immunohistochemical study was performed on human liver specimens from patients with primary biliary cirrhosis (PBC), chronic hepatitis C virus (HCV) infection, submassive cell necrosis, and normal liver. The expression of MDR1, MDR3, BSEP, MRP1, MRP2, and MRP3 was determined using specific antibodies. Dilution series were constructed to determine the critical staining level in order to estimate the factor of up-regulation. In normal liver, hepatocytes showed canalicular staining for MDR3, BSEP, and MRP2. MDR1 stained the canalicular membrane of hepatocytes as well as that of cholangiocytes. MRP3 showed low immunoreactivity of bile duct epithelial cells and centrilobular hepatocytes only. Normal liver showed no immunoreactivity for MRP1. In diseased liver, the expression of MDR3, BSEP, and MRP2 was relatively stable. In PBC, HCV, and submassive necrosis, the expression levels of MDR1, MRP1, and MRP3 were increased. The strongest immunoreactivity was seen after submassive necrosis, where remaining islands of hepatocytes showed strong canalicular staining for MDR1 and MRP3. Regenerating bile ductules at the interface of portal tracts and necrotic areas stained intensely for MDR1, MRP1, and MRP3. In conclusion, MDR1, MRP1, and MRP3 are up-regulated in hepatocytes in severe human liver disease. Strong MDR1, MRP1, and MRP3 reactivity is seen in regenerating human bile ductules. 相似文献
3.
Maria ATC van der Loos Ilse Hellinga Mariska C Vlot Daniel T Klink Martin den Heijer Chantal M Wiepjes 《Journal of bone and mineral research》2021,36(5):931-941
Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin-releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual-energy X-ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed-model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex-specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. 相似文献
4.
Lue?en Henrik. L. de Leeuw Bas. J. Langeme?er Mariska W. E. de Boer A. G. Verhoef J. Coos. Junginger Hans E. 《Pharmaceutical research》1996,13(11):1668-1672
Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin.
Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats.
Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin.
Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs. 相似文献
5.
6.
Nalini Radhakishun Charlotte Blokhuis Mariska van Vliet Ines von Rosenstiel Olivier Weijer Martijn Heymans Jos Beijnen Dees Brandjes Michaela Diamant 《European journal of pediatrics》2014,173(8):1103-1106
The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P?<?0.05). Six weeks after Ramadan, all parameters returned to baseline levels. Conclusion: In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan. 相似文献
7.
Langeveld D Jansen M de Boer DV van Sprundel M Brosens LA Morsink FH Giardiello FM Offerhaus GJ de Leng WW 《Gut》2012,61(6):839-846
8.
9.
Davids M Richir MC Visser M Ellger B van den Berghe G van Leeuwen PA Teerlink T 《Metabolism: clinical and experimental》2012,61(4):482-490
High plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are associated with adverse outcome in critically ill patients. Asymmetric dimethylarginine is released within cells during proteolysis of methylated proteins and is either degraded by dimethylarginine dimethylaminohydrolase (DDAH) or exported to the circulation via cationic amino acid transporters. We aimed to establish the role of DDAH activity in the regulation of tissue and plasma concentrations of ADMA. In 33 critically ill rabbits, we measured DDAH activity in kidney, liver, heart, and skeletal muscle and related these values to concentrations of ADMA in these tissues and in the circulation. Both DDAH activity and ADMA concentration were highest in kidney and lowest in skeletal muscle, with intermediate values for liver and heart. Whereas ADMA content was significantly correlated between tissues (r = 0.40-0.78), DDAH activity was not. Significant inverse associations between DDAH activity and ADMA content were only observed in heart and liver. Plasma ADMA was significantly associated with ADMA in the liver (r = 0.41), but not in the other tissues. In a multivariable regression model, DDAH activities in muscle, kidney, and liver, but not in heart, were negatively associated with plasma ADMA concentration, together explaining approximately 50% of its variation. In critical illness, plasma ADMA poorly reflects intracellular ADMA. Furthermore, tissue DDAH activity is a stronger predictor of plasma ADMA than of intracellular ADMA, indicating that, compared with DDAH activity, generation of ADMA and cationic amino acid transporter-mediated exchange may be more important regulators of intracellular ADMA. 相似文献
10.
Nalini N. E. Radhakishun Mariska van Vliet Ines A. von Rosenstiel Jos H. Beijnen Michaela Diamant 《Pediatric nephrology (Berlin, Germany)》2013,28(7):1145-1149