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1.
Summary The steady-state kinetics of chlorophenoxyisobutyric acid (CPIB) and of bezafibrate were investigated in a strictly controlled, randomised cross-over study in 10 female volunteers, after the conventional oral doses of clofibrate 0.5 g and bezafibrate 0.2 g at 8-h intervals. The mean steady-state concentration of CPIB in serum was 34 times higher than that of bezafibrate, which was due to the considerable cumulation of CPIB, whereas no cumulation of bezafibrate was observed. This is supported by comparison of the AUCs, and of the maximum and mean concentrations of bezafibrate after the first and last doses. (0.44 and 0.49 h–1) and the half-lives (1.6 and 1.4 h) were almost identical after the first and last doses of bezafibrate. The median total clearances of CPIB and bezafibrate amounted to 10.5 and 142.5 ml/min, respectively, if complete absorption of both drugs is assumed. Since the apparent volumes of distribution were in the same range for both drugs, the amount of drug present in the organism in steady-state also differed by a factor of approximately 30 under the usual dosage regimen. 相似文献
2.
目的:研制苯扎贝特缓释微丸胶囊。方法:采用离心造粒技术制备苯扎贝特缓释微丸胶囊;以体外释药和犬的药代动力学参数进行评价。结果:微丸得率86.5%,载药量87.8%;体外释放曲线符合一级方程,相似因子f2为74.23;自制缓释微丸胶囊单剂量犬口服给药后的tmax(3.7±0.5)h,cmax(36.36±0.98)μg/mL,AUC0-∞(337.83±7.29)μg.h/mL;苯扎贝特缓释片(参比片)的tmax(4.1±0.4)h,cmax(39.66±0.94)μg/mL,AUC0-∞(327.27±8.97)μg.h/mL。结论:以进口的缓释片为参比片,自制的苯扎贝特缓释微丸胶囊具有良好的缓释作用;相对生物利用度为(103.3±2.8)%,两种制剂生物等效。 相似文献
3.
Bezafibrate treatment: a new medical approach for PBC patients? 总被引:4,自引:0,他引:4
Background. A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination
ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy. Methods. During a 6-month period, 22 PBC patients with elevated serum alkaline phosphatase (ALP) despite UDCA monotherapy received
either UDCA at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate at 400 mg/day (bezafibrate group). Each patient
underwent detailed clinical and biochemical evaluation. Results. During treatment, changes in ALP level were greater in the bezafibrate group than in the control group (P < 0.01). During and at the end of treatment, serum ALP levels were significantly lower than those before treatment in patients
receiving UDCA plus bezafibrate (P < 0.05). At the end of the 6 months, normalization of serum ALP was observed in 5 of 11 (45.4%) patients given bezafibrate
and in 2 of 11 (18.1%) patients not given bezafibrate (P < 0.16). Bile acid proportions during the combination therapy did not change. Pruritus disappeared in 1 of 7 bezafibrate-group
patients with this symptom. Conclusions. UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered as a new therapeutic option for patients with PBC.
Received: August 22, 2002 / Accepted: November 22, 2002
RID="*"
ID="*" Reprint requests to: T. Kanda 相似文献
4.
5.
The oxidative phosphorylation (OXPHOS) system in mitochondria is responsible for the generation of the majority of cellular energy in the form of ATP. Patients with genetic OXPHOS disorders form the largest group of inborn errors of metabolism. Unfortunately, there is still a lack of efficient therapies for these disorders other than management of symptoms. Developing therapies has been complicated because, although the total group of OXPHOS patients is relatively large, there is enormous clinical and genetic heterogeneity within this patient population. Thus there has been a lot of interest in generating relevant mouse models for the different kinds of OXPHOS disorders. The most common treatment strategies tested in these mouse models have aimed to up-regulate mitochondrial biogenesis, in order to increase the residual OXPHOS activity present in affected animals and thereby to ameliorate the energy deficiency. Drugs such as bezafibrate, resveratrol and AICAR target the master regulator of mitochondrial biogenesis PGC-1α either directly or indirectly to manipulate mitochondrial metabolism. This review will summarize the outcome of preclinical treatment trials with these drugs in mouse models of OXPHOS disorders and discuss similar treatments in a number of mouse models of common diseases in which pathology is closely linked to mitochondrial dysfunction. In the majority of these studies the pharmacological activation of the PGC-1α axis shows true potential as therapy; however, other effects besides mitochondrial biogenesis may be contributing to this as well.
Linked Articles
This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 相似文献6.
Agnes E. La Ville Rosa Solà Claude Motta Núria Plana Mercedes Heras Josep Ribalta Lluís Masana 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1997,11(5):653-658
The effects of bezafibrate, a well-used fibric acid hypolipidemic agent, were investigated in 10 moderately hypertriglyceridemic
patients. The aim was to quantify the physico-chemical modifications to high-density lipoprotein subfraction 3 (HDL3) induced by treatment and to assess, in vitro, the alterations in its principal physiological function, the efflux of intracellular
free cholesterol. Treatment (200mg/thrice/d for 3 months) resulted in a 48% decrease in plasma triglycerides, with an increase
in the HDL cholesterol, due mainly to an increase in the HDL3 (P < 0.01). Composition analysis of HDL3indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and phospholipids (P < 0.01), coupled
with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescense anisotropy at 24°C
was significantly higher post-treatment than pretreatment (P < 0.01). The cholesterol effluxing capacity of pretreatment HDL3 was 28%, and post-treatment this increased to 50% (P < 0.01). Multivariate analyses indicated that the increased capacity
of HDL3 to promote free cholesterol efflux was, in part, due to increased HDL3 phospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering
of plasma triglycerides and that the resultant physico-chemical alterations of the HDL3 molecule make it more efficient as an acceptor of intracellular free cholesterol.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
7.
吴洁 《中国医药工业杂志》2008,39(9)
对氯苯甲酰氯和对羟基苯乙胺反应制得N-(4-羟基苯乙基)-4-氯苯甲酰胺,再在相转移催化剂TEBA作用下、氢氧化钠溶液中加丙酮和氯仿反应制得降血脂药苯扎贝特,总收率约67%。 相似文献
8.
用加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量 总被引:2,自引:0,他引:2
目的:建立加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量。方法:通过方法学验证试验,证明所采用的高效液相色谱法外标法测定苯扎贝特中杂质氯苯酪胺的含量方法可行;再利用外标法,分别测定主成分苯扎贝特和杂质氯苯酪胺的保留时间,计算氯苯酪胺相对于苯扎贝特的相对保留时间,分别测定主成分苯扎贝特和杂质氯苯酪胺的线性方程,以斜率计算杂质氯苯酪胺相对于主成分苯扎贝特的校正因子;最终利用相对保留时间确定杂质氯苯酪胺的位置,用校正因子测定杂质氯苯酪胺的含量。结果:测得杂质氯苯酪胺相对于主成分苯扎贝特的相对保留时间为0.90,校正因子为1.2494。结论:用加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量,方法可行。 相似文献
9.
Summary Two trials have been performed in the same patients with hyperlipoproteinaemia Types IIb (12 cases), III (6 cases) and IV (11 cases). In the first study the lipid-lowering properties of bezafibrate, fenofibrate, gemfibrozil, etofibrate and etofylline clofibrate were compared and in a separate trial the influence of combined treatment with gemfibrozil plus colestipol and bezafibrate plus probucol on lipoproteins were investigated. The mean percentage lipid-lowering effect of each fibrate on serum and VLDL fraction was significant in the Types IIb, III and IV patients, but there were significant differences between the fibrates. In general, gemfibrozil and bezafibrate decreased plasma lipid levels more than etofibrate and etofylline clofibrate in Type IIb patients. In Type IV cases gemfibrozil and bezafibrate were significantly potent in reducing the triglyceride level than fenofibrate, etofibrate or etofylline clofibrate. All the fibrates produced an increase in HDL cholesterol, but there were significant differences between them were in the Type IV patients. The influence of fibrates on the LDL fraction was much more variable. In hyperlipoproteinaemia Type IIb, a decrease in both LDL cholesterol and LDL apolipoprotein B was observed. In Type III and IV patients, however, an increase in LDL concentration occurred. The addition of colestipol to gemfibrozil therapy led to a further decrease in total cholesterol, LDL cholesterol and LDL apolipoprotein B in Type IIb patients. In patients with hyperlipoproteinaemia Types III and IV colestipol prevented the increase in LDL concentration after treatment with gemfibrozil alone. The effect of probucol on LDL cholesterol was comparable to that of colestipol. Combined treatment with gemfibrozil and colestipol caused an increase in HDL cholesterol concentration in contrast to combined treatment with bezafibrate and probucol. It is concluded that combined therapy with fibrates plus bile acid sequestrant would be of practical value in patients with hyperlipoproteinaemia Types IIb, III and IV. 相似文献
10.
The effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) on gastric secretion and gastric cytoprotection was evaluated using five different models of gastric ulcers: acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced gastric ulcers. Bezafibrate, a PPAR-alpha agonist was administered at two different doses of 10 and 100 mg/kg body weight intraperitoneanally. Both doses of bezafibrate showed significant antiulcer effect in ethanol-induced, indomethacin-induced and pylorus ligation-induced gastric ulcers. Bezafibrate increased healing of ulcer in acetic acid-induced chronic gastric ulcer model. Both doses were also effective in preventing gastric lesions induced by ischemia-reperfusion. It was concluded that PPAR-alpha activation increases healing of gastric ulcers and also prevents development of gastric ulcers in rats. 相似文献