全文获取类型
收费全文 | 251篇 |
免费 | 43篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 17篇 |
妇产科学 | 8篇 |
基础医学 | 12篇 |
临床医学 | 45篇 |
内科学 | 49篇 |
皮肤病学 | 1篇 |
神经病学 | 6篇 |
特种医学 | 3篇 |
外科学 | 109篇 |
综合类 | 7篇 |
预防医学 | 5篇 |
眼科学 | 2篇 |
药学 | 28篇 |
肿瘤学 | 1篇 |
出版年
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 6篇 |
2012年 | 15篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 5篇 |
2008年 | 6篇 |
2007年 | 7篇 |
2006年 | 8篇 |
2005年 | 11篇 |
2004年 | 11篇 |
2003年 | 4篇 |
2002年 | 13篇 |
2001年 | 5篇 |
2000年 | 12篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 4篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1972年 | 4篇 |
1971年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有294条查询结果,搜索用时 203 毫秒
1.
2.
Dorit Naot Usha Bava Brya Matthews Karen E Callon Gregory D Gamble Michael Black Sarah Song Rocco P Pitto Tim Cundy Jill Cornish Ian R Reid 《Journal of bone and mineral research》2007,22(2):298-309
Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease. 相似文献
3.
Differences in hip axis and femoral neck length in premenopausal women of Polynesian, Asian and European origin 总被引:4,自引:0,他引:4
There are substantial inter-racial differences in hip fracture incidence. Studies in several different ethnic groups have suggested that differences in the length of the femoral neck may contribute to these. The present study assesses femoral neck and hip axis lengths in three ethnic groups in which it has not been documented previously (Chinese, Indians and Polynesians) and compares these values with those in Europeans. Lengths were measured from dual-energy X-ray absorptiometry scans of the proximal femur in normal premenopausal women (n=225). The Polynesian (1.65 m) and European (1.64 m) women were significantly taller than the two Asian groups (mean height in each, 1.58 m). There were also differences in mean body weight, the Polynesians being the heaviest (76 kg) and the Chinese the lightest (53 kg). Femoral neck lengths were (mean + SD) Chinese 61.5+4.4 mm, Indian 61.5+5.1 mm, Polynesian 68.2+4.3 mm and Europeans 66.0+4.8 mm. Hip axis lengths were Chinese 98.0+5.6 mm, Indian 94.5+5.2 mm, Polynesian 106.4 ± 5.3 mm and European 102.3+5.3 mm. Each of the other groups were significantly different from the Europeans for both variables and, in general, this remained so after height adjustment. These data suggest that shorter femoral necks are common to the major Asian racial groups. However, in contrast to all other ethnic groups studied, Polynesians have longer femoral necks than Europeans and their low incidence of hip fracture is not explicable, therefore, in terms of their femoral neck length. This suggests that either higher bone density or other more subtle differences in proximal femoral geometry must account for the low hip fracture incidence in Polynesians. 相似文献
4.
5.
Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis that results in the production of large quantities of photoactive porphyrins. The clinical syndrome is dominated by extreme photosensitivity with mutilation of light exposed extremities and hemolytic anemia. Bone disease has been occasionally noted, but is not well characterised. We describe a man with CEP who developed bone pain and spinal crush fractures at the age of 22. Skeletal radiographs revealed features typical of other severe hemolytic anemias, but in addition there was loss of the terminal phalanges of the hand as a result of photomutilation. Spinal bone density (assessed by DPA) was reduced and at the hip bone density was at the lower limit of normal. The metacarpal cortical bone density was 2.9 standard deviations below normal. Biochemical and histological studies accelerated bone turnover. Although the serum 250H vitamin D concentration was very low (because of light avoidance) there was no evidence that the bone disease was a consequence of this. Treatment for one year with clodronate and a high transfusion regime was associated with small reductions in serum alkaline phosphatase and urine hydroxyproline excretion, but there was no improvement in bone mineral density. We conclude that CEP has a distinctive osteodystrophy comprising osteolysis of light-exposed extremities and a high turnover type of osteoporosis. Privational vitamin D deficiency may also occur. The effect upon bone of the new therapies for CEP should be considered. 相似文献
6.
Antibodies to cell envelope proteins of Pseudomonas aeruginosa in cystic fibrosis patients. 总被引:4,自引:6,他引:4 下载免费PDF全文
Many vaccines containing somatic and secreted antigens of Pseudomonas aeruginosa have been reported. The vaccines containing lipopolysaccharide have been found to provide type-specific protection, but the endotoxin content of these vaccines does not make it feasible to use them in patients who are already debilitated. Outer membrane proteins could be effective as vaccines, as they can be purified free of lipopolysaccharide, and also because they are common to all serotypes of P. aeruginosa. To be effective as a vaccine, such proteins must be immunogenic and accessible from the outside of the intact bacterial cell. In this study, we showed that systemic antibodies were produced frequently to two cell envelope proteins with masses of 58,500 and 37,500 daltons and occasionally to 34,000-dalton protein of P. aeruginosa in cystic fibrosis patients with chronic lung infections. In rabbits immunized with whole, fixed cells of P. aeruginosa, antibodies were also produced against the 58,500-dalton proteins. Thus, the 58,500-dalton cell envelope protein of P. aeruginosa was the only immunogenic protein that was accessible to the immune system when whole, fixed cells were used for immunization. These serum antibodies did not protect the cystic fibrosis patients against further lung infection with P. aeruginosa. 相似文献
7.
A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype 总被引:5,自引:0,他引:5
8.
9.
Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. 总被引:12,自引:1,他引:12 下载免费PDF全文
R Kohen Y Yamamoto K C Cundy B N Ames 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(9):3175-3179
Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle. 相似文献
10.