全文获取类型
收费全文 | 1859篇 |
免费 | 84篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 51篇 |
儿科学 | 7篇 |
妇产科学 | 20篇 |
基础医学 | 301篇 |
口腔科学 | 26篇 |
临床医学 | 121篇 |
内科学 | 467篇 |
皮肤病学 | 23篇 |
神经病学 | 279篇 |
特种医学 | 39篇 |
外科学 | 211篇 |
综合类 | 9篇 |
预防医学 | 55篇 |
眼科学 | 9篇 |
药学 | 137篇 |
中国医学 | 5篇 |
肿瘤学 | 188篇 |
出版年
2023年 | 3篇 |
2022年 | 14篇 |
2021年 | 12篇 |
2020年 | 14篇 |
2019年 | 12篇 |
2018年 | 20篇 |
2017年 | 11篇 |
2016年 | 8篇 |
2015年 | 15篇 |
2014年 | 19篇 |
2013年 | 37篇 |
2012年 | 104篇 |
2011年 | 125篇 |
2010年 | 41篇 |
2009年 | 35篇 |
2008年 | 91篇 |
2007年 | 133篇 |
2006年 | 110篇 |
2005年 | 148篇 |
2004年 | 142篇 |
2003年 | 118篇 |
2002年 | 119篇 |
2001年 | 59篇 |
2000年 | 51篇 |
1999年 | 55篇 |
1998年 | 23篇 |
1997年 | 21篇 |
1996年 | 25篇 |
1995年 | 21篇 |
1994年 | 26篇 |
1993年 | 23篇 |
1992年 | 39篇 |
1991年 | 46篇 |
1990年 | 26篇 |
1989年 | 38篇 |
1988年 | 24篇 |
1987年 | 22篇 |
1986年 | 25篇 |
1985年 | 15篇 |
1984年 | 20篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1969年 | 3篇 |
排序方式: 共有1948条查询结果,搜索用时 15 毫秒
1.
2.
A 68-year-old man had subacute cerebellar degeneration and a non-Hodgkin's lymphoma. Using an immunoblotting method, we found serum antibodies to rat cerebral 250-kd and 110-kd and cerebellar 110-kd acidic cytoplasmic proteins. The antibodies did not react unless the antigens were prepared soon after death with protease inhibitors. Two hundred fifty-kd and 110-kd proteins are minor components of soluble cytoplasmic proteins of the brain. The molecular weights differed from other soluble brain-specific proteins already characterized. 相似文献
3.
We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome. 相似文献
4.
A. Robert Spitzer Shalom Stahl David Yarnitsky Ernest W. Johnson John R. Wilson R. A. C. Hughes Stefania Morino Giovanni Antonini Kiyotoshi Kaneko Yoji Ohnishi Tetsushi Atsumi Isao Hozumi Tadashi Miyatake Tetsuo Furukawa James P. Knochel Ikuo Mineo Seiichiro Tarui Francis O. Walker Andrew J. Gitter Walter C. Stolov Nicholas J. Capozzoli 《Muscle & nerve》1996,19(4):531-538
5.
Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage. 总被引:5,自引:0,他引:5
Kazuto Hoshi Naoshi Ogata Takashi Shimoaka Yasuo Terauchi Takashi Kadowaki Shin-Ichi Kenmotsu Ung-Il Chung Hedehiro Ozawa Kozo Nakamura Hiroshi Kawaguchi 《Journal of bone and mineral research》2004,19(2):214-223
Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa. 相似文献
6.
Yu-Yan Fan Ryoko Baba Yukiko Nagai Akira Miyatake Naohisa Hosomi Shoji Kimura Guang-Ping Sun Masakazu Kohno Mamoru Fujita Youichi Abe Akira Nishiyama 《Hypertension research》2006,29(3):169-178
Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury. 相似文献
7.
Akihiko Hashi Tsutomu Yuminamochi Shin-Ichi Murata Hideki Iwamoto Tsuyoshi Honda Kazuhiko Hoshi 《International journal of gynecological pathology》2003,22(4):374-377
Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum. 相似文献
8.
Miya Yoshino Hidetoshi Yamazaki Hisahiro Yoshida Shumpei Niida Shin-Ichi Nishikawa Kazuo Ryoke Takahiro Kunisada Shin-Ichi Hayashi 《Journal of bone and mineral research》2003,18(1):108-116
Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice. 相似文献
9.
Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta. 总被引:1,自引:0,他引:1
Masataka Oitate Takashi Hirota Takahiro Murai Shin-Ichi Miura Toshihiko Ikeda 《Drug metabolism and disposition》2007,35(10):1846-1852
In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations. 相似文献
10.
Paul Hechenleitner Walter Mark Daniel Candinas Tsukasa Miyatake Nozomi Koyamada Wayne W. Hancock Fritz H. Bach 《Xenotransplantation》1996,3(4):279-286
Abstract: Accommodation refers to survival of a xenograft despite the presence of anti-donor organ antibodies and complement. We have recently shown that accommodation of a hamster heart transplanted to a rat receiving short-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of "protective" genes, ii) a prominent intragraft Th2 cytokine profile, and iii) the relatively heavy deposition of IgG2c antibodies on the EC of the graft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of IgG2c. These findings are consistent with host factors (Th2 cytokines and IgG2c) contributing to xenograft accommodation. To test whether these host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a surviving first heart; recipients were, at the time, receiving only CyA. Whereas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days, and the other survived for 7 days. Nine of the twelve were not rejected: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving second hearts we studied had accommodated in that the picture on immunopathology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing prolonged survival of the second grafts and, further, that these factors contribute to the expression in the EC and smooth muscle cells of the surviving second hearts of the protective genes. 相似文献