全文获取类型
收费全文 | 3382篇 |
免费 | 143篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 24篇 |
儿科学 | 62篇 |
妇产科学 | 41篇 |
基础医学 | 437篇 |
口腔科学 | 162篇 |
临床医学 | 240篇 |
内科学 | 884篇 |
皮肤病学 | 33篇 |
神经病学 | 144篇 |
特种医学 | 52篇 |
外科学 | 577篇 |
综合类 | 32篇 |
预防医学 | 76篇 |
眼科学 | 28篇 |
药学 | 299篇 |
中国医学 | 6篇 |
肿瘤学 | 440篇 |
出版年
2022年 | 16篇 |
2021年 | 40篇 |
2020年 | 19篇 |
2019年 | 38篇 |
2018年 | 40篇 |
2017年 | 29篇 |
2016年 | 39篇 |
2015年 | 41篇 |
2014年 | 86篇 |
2013年 | 96篇 |
2012年 | 129篇 |
2011年 | 138篇 |
2010年 | 69篇 |
2009年 | 83篇 |
2008年 | 140篇 |
2007年 | 133篇 |
2006年 | 126篇 |
2005年 | 144篇 |
2004年 | 140篇 |
2003年 | 123篇 |
2002年 | 110篇 |
2001年 | 109篇 |
2000年 | 123篇 |
1999年 | 116篇 |
1998年 | 48篇 |
1997年 | 35篇 |
1996年 | 36篇 |
1995年 | 28篇 |
1994年 | 29篇 |
1993年 | 25篇 |
1992年 | 116篇 |
1991年 | 104篇 |
1990年 | 116篇 |
1989年 | 84篇 |
1988年 | 80篇 |
1987年 | 101篇 |
1986年 | 105篇 |
1985年 | 88篇 |
1984年 | 44篇 |
1983年 | 46篇 |
1981年 | 19篇 |
1979年 | 46篇 |
1978年 | 19篇 |
1977年 | 22篇 |
1976年 | 19篇 |
1975年 | 18篇 |
1974年 | 17篇 |
1973年 | 23篇 |
1972年 | 20篇 |
1969年 | 18篇 |
排序方式: 共有3537条查询结果,搜索用时 15 毫秒
1.
Shiro Akinaga Tadashi Ashizawa Katsushige Gomi Hiroe Ohno Makoto Morimoto Chikara Murakata Masami Okabe 《Cancer chemotherapy and pharmacology》1992,29(4):266-272
Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca2+-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases. 相似文献
2.
K Takeuchi O Furukawa H Tanaka H Nishiwaki S Okabe 《Japanese journal of pharmacology》1987,44(2):163-170
The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10(-4) M HCl, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCl. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (approximately 8 microEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16-dimethyl prostaglandin E2 (16-dmPGE2: 30 micrograms/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCl for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 significantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of HE on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins. 相似文献
3.
Tatsurou Tanaka Yasuhiro Morimoto Hiroshi Takano Kazuhiro Tominaga Shinji Kito Sachiko Okabe Tetsu Takahashi Jin-ichi Fukuda Takeshi Ohba 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2005,100(5):609-613
OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium. 相似文献
4.
We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers. 相似文献
5.
Yoshinobu Okabe Osamu Tsuruta Yoshiki Naito Hideya Suga Michio Sata 《Digestive endoscopy》2007,19(Z1):S121-S125
Regarding peroral cholangioscopy (POCS) for biliary disease, due to the recent appearance of a video cholangioscope that can obtain high‐quality images, it is possible to observe subtle changes of the biliary mucosa. In addition to the conventional observation method using POCS, the biliary mucosa with also observed with narrow band imaging (NBI) in one case of chronic cholangitis and four cases of extra hepatic bile duct tumor (three surgical cases). In the conventional observation method, the vessels in the surface layer of the biliary mucosa could be observed more clearly using NBI. In one case in which a tumor was observed, the irregularity of the biliary mucosa became clear on NBI, and the vessels inside a papillary tumor could also be easily observed. In another case of bile duct tumor, the conventional observation method showed a region in the proximity of the tumor where the vessels could not be seen clearly, but they could be seen clearly on NBI. In all of the cases, the bile juice was seen as red on NBI, which disturbed the observation. With POCS using NBI, it was possible to observe the vessels and irregularities in the surface layer of the biliary mucosa more clearly than with conventional observation methods. 相似文献
6.
7.
8.
K Takeuchi T Ohuchi H Miyake H Sugawara S Okabe 《Japanese journal of pharmacology》1992,60(3):303-305
The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis. 相似文献
9.
The time-course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the effects on it of 16,16-dimethyl prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 hr after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3, 30 micrograms/kg), papaverine (100 mg/kg) and atropine (1 mg/kg) protected the surface cells against stress (1 hr)-induced damage, and inhibited visible lesion formation after 4 hr stress. Timoprazole (30 mg/kg, s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. dmPGE2, papaverine and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. dmPGE2, timoprazole and atropine, but not papaverine, inhibited acid secretion in stress-conditions. These results indicated that stress induced damage to the gastric mucosa within 1 hr due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions. 相似文献
10.
Tissue samples from 30 patients with adenoid cystic carcinoma and 20 with adenocarcinoma of salivary gland origin were studied by immunohistochemical staining with specific antibodies to the four macromolecules that are present in normal basement membranes: type IV collagen, laminin, heparan sulfate proteoglycan, and entactin. In the adenoid cystic carcinoma samples, the four proteins were localized in different types of extracellular matrices in the tumor, namely pseudocystic spaces, hyaline stroma, and around tumor cell nests. The staining intensity was enhanced by pretreatment with hyaluronidase. The tumor cells of adenoid cystic carcinoma showed a tendency to proliferate with individual cells in contact with the basement membrane and to infiltrate through basement membrane-rich tissues, such as peripheral nerves, blood vessels, and skeletal muscles. In contrast, only circumferential staining of tumor cell nests was obtained in adenocarcinoma samples. The results suggest that adenoid cystic carcinoma is a tumor with affinity for basement membranes, and this basic feature is reflected in its histology and presumably in its biologic behavior. Immunostaining with antibodies to basement membrane proteins appears to be useful for differential diagnosis of some types of these two carcinomas. 相似文献