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71.
Sakanaka K Kawazu K Nishida K Nakamura J Nakashima M Nakamura T Oshita A Ichikawa N Sasaki H 《Biological & pharmaceutical bulletin》2006,29(10):2143-2147
The purpose of this study is to characterize the transport of tilisolol and timolol through the corneal epithelium, which is believed to be a tight barrier of ocular drug absorption. Cultured normal rabbit corneal epithelial cells (RCEC) were used to investigate drug transport. Primary RCEC were seeded on a filter membrane of Transwell-COL insert coated with fibronectin and grown in Dulbecco's modified Eagle's medium/nutrient mixture F-12 with various supplements. Beta-blocker permeability through the RCEC layer was measured to assess the transcellular permeability coefficient (P(transcell)) in the absence or presence of inhibitors. The transcellular permeability of tilisolol was dependent on drug concentration although timolol showed no concentration dependency. Tilisolol flux from the apical to the basal side was larger than in the opposite direction although timolol showed no direction dependency. The transcellular permeability of tilisolol from the apical to the basal side was inhibited by sodium azide, tetraethylammonium, quinidine, taurocholic acid, guanidine and carnitine. Tilisolol had an active mechanism in uptake to the corneal epithelium, probably by the organic cation transporter family, although timolol predominantly permeated via passive diffusion. This RCEC system was useful to characterize the ocular permeation mechanism of drugs. 相似文献
72.
PEGylated liposomes loading palmitoyl prednisolone for prolonged blood concentration of prednisolone
Teshima M Kawakami S Fumoto S Nishida K Nakamura J Nakashima M Nakagawa H Ichikawa N Sasaki H 《Biological & pharmaceutical bulletin》2006,29(7):1436-1440
We investigated the pharmacokinetic behavior of palmitoyl prednisolone (Pal-PLS) and its liposomes with L-alpha-distearoylphosphatidylcholine (DSPC) and cholesterol (Chol) with or without L-alpha-distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000) after their intravenous administration in rats. Pal-PLS rapidly disappeared from the systemic circulation and prednisolone (PLS) was regenerated after the administration of DSPC/Chol liposomes. PEGylated liposomes including DSPE-PEG 2000, however, successfully maintained high blood concentrations of Pal-PLS and PLS. The blood profiles of drugs after the administration of liposomal Pal-PLS were analyzed according to a two-compartment model. The larger content of DSPE-PEG 2000 in DSPC/Chol liposomes showed a lower first order elimination rate constant from the central compartment (K(el)) and clearance (CL). The area under the concentration-time curve (AUC) of Pal-PLS and PLS in PEGylated liposomes was larger than DSPC/Chol liposomes. The mean resident time (MRT) of Pal-PLS and PLS was also prolonged by PEGylated liposomes. Although DSPC/Chol liposomes showed a high distribution of Pal-PLS in the liver and spleen, PEGylated liposomes significantly decreased the liver distribution of Pal-PLS. The biliary and urinary excretions of drugs for 240 min after drug administration were less than 1% of the administrated dose in any formulations. In conclusion, PEGylated liposomes, including Pal-PLS, are useful for maintain the PLS concentration in the blood after intravenous administration. 相似文献
73.
K Naka S Toguchi T Takaishi H Ishizu Y Sasaki 《The International journal of social psychiatry》1985,31(4):267-274
This study reports on the relations between the yuta (shaman) and the community mental health activities on Okinawa, Japan. Focus is on the process of initiation of the yuta and its meanings from the mental health viewpoints, the functions of the yuta in the particular cultural background of the island, and the importance of admitting the existence of the yuta in its relations to the psychiatric treatment in a mental hospital. The discussion is based on the authors' research findings which were obtained mostly through their therapeutic activities and their field studies. The authors' assumption is that each culture has in it a certain social background that is unique in that culture by which a stress or insanity is increased or brought about, but in the same culture there are ways to decrease the stress and to cure the insanity. 相似文献
74.
A Masuda P E Paulev Y Sakakibara B Ahn S Takaishi M Pokorski Y Nishibayashi Y Honda 《The Japanese journal of physiology》1988,38(5):607-618
Nine normal male subjects were studied at three levels of exercise (0, 40, and 80 W). Single vital capacity breath test was applied at rest and during exercise (phases 2 and 3). Minimum minute ventilation found within 4 breaths following the test was compared to the control value. Significant depression in minute ventilation was invariably observed. The minute ventilation was depressed more and more with increasing intensity of exercise. A significant difference was found between exercise and rest. However, the relative contribution of chemoreceptor activity remained the same 10-20% at all exercise levels. The magnitude of ventilatory depression (delta V resp) in phase 2 was larger than that in phase 3, when work rate increased to 80 W, both relative and absolute. A significant part of the exercise hyperpnea is due to peripheral chemoreceptor activity. The peripheral chemoreceptor activity is greater in phase 2 than in phase 3 at work rates of light to moderate intensity. 相似文献
75.
Nishida K Fujiwara R Kodama Y Fumoto S Mukai T Nakashima M Sasaki H Nakamura J 《Pharmaceutical research》2005,22(8):1331-1337
Purpose The purpose of this study was to examine drug distribution in the liver after drug application to the rat liver surface.Methods Phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextran (MW 4400, FD-4) as model compounds or 5-fluorouracil (5-FU) was applied to the rat liver surface by employing a cylindrical diffusion cell (i.d. 9 mm, 0.64 cm2). Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites: the region under the diffusion cell attachment site (site 1), the applied lobe except for site 1 (site 2), and non-applied lobes (site 3).Results In the case of i.v. administration, there were no differences in PSP concentrations among the three sites of the rat liver, and the concentrations rapidly decreased. On the other hand, the PSP concentration in site 1 after application to the rat liver surface was considerably higher than in site 2 and site 3. In addition, the area under the curve (AUC) value (AUCsite1), calculated from the PSP concentration profile in site 1, was about 10 times larger than that in site 3. A similar trend of regional delivery advantage by liver surface application was observed in the case of the macromolecule model FD-4, with a marked AUCsite1 of about 5 times larger than the other two sites. Moreover, we clarified that the anticancer drug 5-FU preferentially distributed in site 1 after application to the rat liver surface.Conclusion These results demonstrate the possibility of regional delivery of drugs to the liver by application to the liver surface. 相似文献
76.
Hirayama R Nishida K Fumoto S Nakashima M Sasaki H Nakamura J 《Biological & pharmaceutical bulletin》2005,28(1):181-184
We developed a gene transfer following the administration of naked plasmid DNA (pDNA) to the kidney surface in mice, and found that the luciferase levels produced in the applied kidney were significantly higher than those produced in another kidney. In contrast, stable renal gene expression was not observed in the case of intraperitoneal or intravenous administration of pDNA. The level of gene expression after instillation of pDNA to the kidney surface reached maximum at 12 h and gradually diminished thereafter. The production of luciferase was saturated at 5 microg of pDNA, and was not affected by instillation volume. Furthermore, pDNA uptake from the kidney surface was proved by in situ experiments using a glass-made diffusion cell. We demonstrated a novel unilateral kidney-selective gene transfer following the administration of naked pDNA to the kidney surface in mice. 相似文献
77.
Ishii K Matsumoto M Momoshima S Watanabe K Tsuji T Takaishi H Nakamura M Toyama Y Chiba K 《Spine》2011,36(4):E256-E262
78.
79.
Morohoshi Y Matsuoka K Chinen H Kamada N Sato T Hisamatsu T Okamoto S Inoue N Takaishi H Ogata H Iwao Y Hibi T 《Journal of gastroenterology》2006,41(4):318-324
Background Neutrophil elastase (NE) is a major secretory product from activated neutrophils and a major contributor to tissue destruction.
However, little is known about the pathogenic contribution of NE to ulcerative colitis (UC). This study was designed to investigate
the contribution of NE by measuring NE activity in plasma and colonic mucosal tissue from UC patients and a murine acute colitis
model, and to elucidate the therapeutic effect of the NE-specific inhibitor ONO-5046.
Methods The NE enzyme activities in plasma and colonic mucosal tissue from UC patients were directly measured using an enzyme–substrate
reaction. Acute colitis was induced in mice by administration of 1.5% dextran sulfate sodium (DSS) for 5 days. DSS-induced
colitis mice were then treated with ONO-5046 (50 mg/kg body weight) intraperitoneally twice a day.
Results In UC patients, the NE enzyme activity was significantly elevated in both the plasma and colonic mucosal tissue compared with
healthy controls. In DSS-induced colitis mice, the NE enzyme activity increased in parallel with the disease development.
ONO-5046 showed therapeutic effects in DSS-treated mice by significantly reducing weight loss and histological score. ONO-5046
suppressed the NE enzyme activities in both plasma and culture supernatant of colonic mucosa from DSS-induced colitis mice.
Conclusions ONO-5046, a specific NE inhibitor, prevented the development of DSS-induced colitis in mice. NE therefore represents a promising
target for the treatment of UC patients. 相似文献
80.
Hikata T Takaishi H Takito J Hakozaki A Furukawa M Uchikawa S Kimura T Okada Y Matsumoto M Yoshimura A Nishimura R Reddy SV Asahara H Toyama Y 《Blood》2009,113(10):2202-2212