全文获取类型
收费全文 | 172篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
丛书文集 | 1篇 |
现状及发展 | 62篇 |
研究方法 | 24篇 |
综合类 | 75篇 |
自然研究 | 11篇 |
出版年
2018年 | 2篇 |
2017年 | 1篇 |
2012年 | 6篇 |
2011年 | 17篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 6篇 |
2007年 | 2篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 6篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1964年 | 2篇 |
1959年 | 2篇 |
1955年 | 1篇 |
排序方式: 共有173条查询结果,搜索用时 15 毫秒
91.
Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition 总被引:4,自引:0,他引:4
Mao JR Taylor G Dean WB Wagner DR Afzal V Lotz JC Rubin EM Bristow J 《Nature genetics》2002,30(4):421-425
Tenascin-X is a large extracellular matrix protein of unknown function. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts. 相似文献
92.
93.
Bone and haematopoietic defects in mice lacking c-fos. 总被引:26,自引:0,他引:26
Z Q Wang C Ovitt A E Grigoriadis U M?hle-Steinlein U Rüther E F Wagner 《Nature》1992,360(6406):741-745
94.
Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase. 总被引:20,自引:0,他引:20
Cystic fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. These channels in normal cells are activated by cyclic AMP-dependent protein kinase and protein kinase C. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2(+)-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2(+)-dependent activation. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. 相似文献
95.
Insights from von Willebrand disease animal models 总被引:5,自引:0,他引:5
von Willebrand disease is a genetic bleeding disorder that arises from abnormalities in von Willebrand factor, an adhesive glycoprotein involved in both primary hemostasis and coagulation. It is the most common inherited bleeding disorder in humans, and over the years several animal species have also been described as suffering from this disease whether through a spontaneous mutation (pigs, dogs) or a genetically engineered one (mouse). These different animal models are extremely useful in exploring the characteristics of von Willebrand disease and in testing new treatments. This review provides an update of the various von Willebrand disease models and the contribution that these models can make to a better understanding of human von Willebrand disease. 相似文献
96.
97.
Conserved function for embryonic nodal cilia 总被引:10,自引:0,他引:10
How left right handedness originates in the body plan of the developing vertebrate embryo is a subject of considerable debate. In mice, a left right bias is thought to arise from a directional extracellular flow (nodal flow) that is generated by dynein-dependent rotation of monocilia on the ventral surface of the embryonic node. Here we show that the existence of node monocilia and the expression of a dynein gene that is implicated in ciliary function are conserved across a wide range of vertebrate classes, indicating that a similar ciliary mechanism may underlie the establishment of handedness in all vertebrates. 相似文献
98.
Summary The inhibitory actions of -ergocryptin on fertility and lactation in the rat are altered differentially in the 2-bromo derivative of this ergot alcaloid. It is therefore unlikely that the fertility inhibiting and the lactation inhibiting effects of 2-bromo--ergocryptin are governed by a single mechanism of action. 相似文献
99.
Reactive hyperemic responses of the coronary arterial bed, provoked by asphyxia or clamping of the coronary artery, were compared in alloxan-diabetic and metabolically healthy dogs. In alloxan-diabetic dogs the response of the coronary arterial bed lasted longer, and its reactivity to hypoxia was lower. Treatment with adenosine caused less vasodilation in diabetic animals than in controls. These changes may be due to the altered reactivity of diabetic vascular smooth muscle. 相似文献
100.
Auwerx J Avner P Baldock R Ballabio A Balling R Barbacid M Berns A Bradley A Brown S Carmeliet P Chambon P Cox R Davidson D Davies K Duboule D Forejt J Granucci F Hastie N de Angelis MH Jackson I Kioussis D Kollias G Lathrop M Lendahl U Malumbres M von Melchner H Müller W Partanen J Ricciardi-Castagnoli P Rigby P Rosen B Rosenthal N Skarnes B Stewart AF Thornton J Tocchini-Valentini G Wagner E Wahli W Wurst W 《Nature genetics》2004,36(9):925-927
The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease. 相似文献