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排序方式: 共有295条查询结果,搜索用时 218 毫秒
1.
Hideaki Ban Hiroyuki Kato Tsutomu Araki Hideaki Fujikura Yoshinari Hasegawa Kyuya Kogure 《Brain research》1994,646(2)
We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyl-adenosine (CHA), [3H]MK-801, and [3H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABAA) receptors, respectively. [3H]PN200-110 labeled L-type Ca2+ channels. [3H]Forskolin, [3H]cyclic adenosine monophosphate (cAMP), [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-triphosphate (IP3) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP3 receptors, respectively. Approximately 20% reductions in [3H]QNB, [3H]forskolin, and [3H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [3H]CHA, [3H]MK-801, [3H]muscimol, [3H]PN200-110, [3H]cAMP, and [3H]IP3 binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications. 相似文献
2.
Hiroyuki Motoie Atsushi Okazaki Hiroyuki Kanoh Hisataka Shikama Takashi Fujikura 《Basic & clinical pharmacology & toxicology》1997,81(1):42-47
Abstract: We have evaluated the relationship between bone mass and mechanical properties of bone from male and female rats treated with YM175, a novel bisphosphonate, for 104 weeks. YM175 [disodium (cycloheptylamino) methylenediphosphonate monohydrate] was given via the drinking water at a concentration of 0, 0.005, 0.015, 0.05, or 0.15%. Since the mortality in the male 0.15% group exceeded the exclusion criteria (75%) at week 88, this group was omitted from the study. Mean daily intake of YM175 was 2.2-22.1 mg/kg for males and 3.6-104 mg/kg for females. After the treatment, mechanical properties and ash weight of the humerus were determined. In males, 0.015 and 0.05% of YM175 (6.6–22.1 mg/kg) significantly increased failure load of the midshaft. In females, failure load and stiffness of the midshaft tended to be increased by YM175 (up to 104 mg/kg). Furthermore, ultimate compressive load at the humeral metaphysis treated with the highest dose of YM175 was 2- or 3.5-fold greater than that of untreated male or female control. Ash weight of the humerus was increased dose-dependently and was positively correlated with failure load of the midshaft. These findings indicate that treatment for 2 years with YM175 increased bone mass and mechanical strength without blocking bone mineralization. 相似文献
3.
Euy Kyun Shin Fumihiko Matsuda Junji Fujikura Takashi Akamizu Hideo Sugawa Toru Mori Tasuku Honjo 《European journal of immunology》1993,23(9):2365-2367
In an Epstein-Barr virus-transformed human B cell line we found an unusual immunoglobulin heavy chain gene rearrangement. Restriction mapping and sequencing analysis led us to conclude that VH-D and D-JH recombination took place in a single allele. Both VH-D and D-JH complexes still had their recombination signal sequences adjacent and the DNA sandwiched by these two complexes retained a germ line configuration, suggesting the potential for a secondary rearrangement resulting in a VH-D(-D)-JH formation. With this finding, we propose a novel pathway, in which the VH-D complex is an intermediate in the formation of a functional VH exon. 相似文献
4.
The effects of FK506, a new immunosuppressive agent, on the rat thymus were investigated using the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies. Flow cytometric analysis of the thymus revealed that the proportion of cells labelled positively with OX7 (Thy-1 antigen), OX8 (CD8, T cytotoxic/suppressor cells) and W3/25 (CD4, T helper cells and macrophages) increased following treatment, with FK506, 1 mg/kg body weight for 14 days. A marked reduction of the thymic medulla following treatment was clearly demonstrated by staining with OX18 (MHC class I) and OX6 (MHC class II). Changes produced by FK506 were also observed in the cortical area of the thymus, being especially marked in the subcapsular area and around the blood vessels by staining with OX6, PKK-1 (alpha-cytokeratin), AB-1040 (type IV collagen), and AB-1220 (laminin). Eventually FK506 treatment resulted in patchy reduction of OX-6, PKK-1, AB-1040 and AB-1220 positive area in the cortex. This evidence suggests that FK506 may impair the thymic microenvironment and subsequently disturb the thymocyte maturation. 相似文献
5.
Hiroyuki Yasui Kiyoshi Yamaoka Terumichi Nakagawa 《Journal of pharmacokinetics and pharmacodynamics》1995,23(2):183-203
A new hepatocellular diffusion model was developed to kinetically evaluate the hepatobiliary transport processes of drugs
in the perfusion system, based on the physiological structure of the liver. Since the equations describing the hepatocellular
diffusion phenomena were derived as image forms in the Laplace domain, the fast inverse Laplace transform (FILT) was adopted
to manipulate the image equations. Cefixime and cefpiramide were selected as model drugs. The concentrations in the perfusate
and the excreted amounts into the bile were simultaneously measured at appropriate intervals after the rapid administration
of each drug into the portal vein. The hepatocellular diffusion model was fitted to the biliary excretion profiles from rat
livers, by means of a nonlinear least squares program, MULTI(FILT). According to this model, the hepatobiliary transport process
of drug is kinetically separated into three steps, that is, the diffusion into and through the hepatocytes, the transfer from
the hepatocytes into the bile canaliculi, and the movement through the bile canaliculi to the outlet of bile duct. These steps
are characterized by the diffusion rate constant through hepatocytes (kdif), the permeability rate constant into the bile canaliculi (kbmc) and the transit time through the bile canaliculi to the outlet of bile duct (
), respectively. It was demonstrated that kdif of cefixime (0.023min1) was significantly smaller than that of cefpiramide (0.044 min1), while the differences in kbmc and
were not obvious between cefixime and cefpiramide. kbmc and
of both drugs were about 1.2 min1 and about 1.0 min, respectively. These parameters were correlated to the excretion ratio into the bile (Fbile) and the mean transit time from the sinusoid through the hepatocytes to the outlet of bile duct (
). 相似文献
6.
Ideyama Y Kudoh M Tanimoto K Susaki Y Nanya T Nakahara T Ishikawa H Fujikura T Akaza H Shikama H 《Japanese journal of pharmacology》1999,79(2):213-220
The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity. 相似文献
7.
Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations 总被引:13,自引:0,他引:13
Kiyoshi Yamaoka Terumichi Nakagawa Toyozo Uno 《Journal of pharmacokinetics and pharmacodynamics》1978,6(2):165-175
According to linear pharmacokinetics, the time course of plasma concentration of a drug, Cp,is expressed by a sum of exponential functions, Cp=
i=1
n
ai
.This article describes a statistical technique to estimate the number of exponential terms, n,for the time course of drug by the application of Akaike's information criterion (AIC). Plasma concentrations of ethoxybenzamide, sulfisoxazole, bishydroxycoumarin, and diazepam measured following bolus intravenous injection were used as clinical examples for this method. Selection of models is compared between the AIC method and an Ftest method at significance levels of 5% and 1%. 相似文献
8.
Kazuo Imai Takuya Maeda Yusuke Sayama Kei Mikita Yuji Fujikura Kazuhisa Misawa Morichika Nagumo Osamu Iwata Takeshi Ono Ichiro Kurane Yasushi Miyahira Akihiko Kawana Sachio Miura 《Emerging infectious diseases》2014,20(1):146-148
We report a patient with congenital Chagas disease in Japan. This report reemphasizes the role of neglected and emerging tropical diseases in the era of globalization. It also indicates the need for increased vigilance for detecting Chagas disease in non–disease-endemic countries. 相似文献
9.
10.