全文获取类型
收费全文 | 436篇 |
免费 | 35篇 |
出版年
2017年 | 5篇 |
2015年 | 12篇 |
2014年 | 16篇 |
2013年 | 21篇 |
2012年 | 17篇 |
2011年 | 9篇 |
2010年 | 8篇 |
2009年 | 14篇 |
2008年 | 11篇 |
2007年 | 11篇 |
2006年 | 16篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 5篇 |
1998年 | 11篇 |
1995年 | 3篇 |
1992年 | 8篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 11篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 12篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1972年 | 3篇 |
1971年 | 10篇 |
1970年 | 10篇 |
1969年 | 5篇 |
1968年 | 3篇 |
1965年 | 3篇 |
1948年 | 5篇 |
1947年 | 5篇 |
1945年 | 3篇 |
1943年 | 5篇 |
1942年 | 4篇 |
排序方式: 共有471条查询结果,搜索用时 234 毫秒
1.
2.
3.
Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II 总被引:12,自引:0,他引:12
A J Reuser M Kroos R P Oude Elferink J M Tager 《The Journal of biological chemistry》1985,260(14):8336-8341
Glycogenosis type II is an inherited lysosomal storage disease with acid alpha-glucosidase deficiency as the primary defect. Using cultured skin fibroblasts, we have studied the biosynthesis of acid alpha-glucosidase in clinically different forms of this disease. Three unrelated patients were identified (one with an infantile, one with a juvenile, and one with an adult form of the disease) producing normal quantities of the 110-kDa precursor form of acid alpha-glucosidase. However, post-translational modification to mature 76-kDa enzyme protein was either completely deficient or extremely inefficient. No abnormalities were observed in glycosylation of the mutant precursors, as measured by the incorporation of [3H]mannose, but phosphorylation was only detectable for the precursor synthesized by fibroblasts from the juvenile patient. In three other patients (one with a juvenile and two with adult forms of glycogenosis type II) apparently reduced synthesis of precursor protein was observed, but the processing to mature enzyme seemed to be undisturbed. Finally, neither precursor nor mature forms of acid alpha-glucosidase were detectable in one particular case of infantile glycogenosis type II. The studies reveal an unexpected degree of genetic heterogeneity in this disease and identify various mutants which could be of importance to further elucidate the biosynthetic events during lysosomal enzyme formation. 相似文献
4.
5.
6.
7.
Disposition of the phenylalanine B25 side chain during insulin-receptor and insulin-insulin interactions 总被引:1,自引:0,他引:1
By the semisynthesis of both full-length insulin analogues and their des-pentapeptide-(B26-B30)-alpha-carboxamide counterparts, we have examined the importance of the electronic character and bulk of the position B25 side chain both in directing insulin interaction with its receptor on isolated canine hepatocytes and in determining the ability of insulin to self-associate in solution. Analogues include those in which PheB25 was replaced by cyclohexyl-Ala; Tyr; p-nitro-, p-fluoro-, p-iodo-, or p-amino-Phe; or p-amino-Phe in which the aromatic amino function had been acylated by the acetyl, hexanoyl, decanoyl, or 1-adamantanoyl group. Our findings identify that (a) the beta-aromatic side chain at position B25 is indeed critical for high-affinity ligand-receptor interactions, (b) neither electron withdrawal from nor electron donation to the beta-aromatic ring perturbs ligand-receptor interactions in major ways, (c) considerable latitude is allowed the placement of linear or polycyclic apolar mass at the para position in p-amino-PheB25-substituted analogues with respect both to receptor binding affinity and to biological activity in vivo, and (d) para apolar mass at position B25 is readily accommodated during the self-association of insulin monomers, as assessed by analytical tyrosine radioiodination and spectroscopic analysis of analogue complexes with Co2+ and Co3+. These findings are discussed in terms of a model for insulin-receptor interactions at the cell membrane in which the position B25 side chain defines the edge of intermolecular contact. 相似文献
8.
Analysis of glucagon and deshistidine glucagon binding to isolated canine hepatocytes and to hepatocyte membrane vesicles (formed by budding of hepatocytes in hypotonic medium) reveals two separate populations of hormone binding sites. Mathematical modeling further shows that the high affinity population represents 1% of the total in all four cases. Although calculated dissociation constants for hormone binding range from 0.2 to 400 nM, whether considering glucagon or deshistidine glucagon binding, or binding to the high affinity or low affinity receptor populations, receptor affinity increases 2- to 100-fold in the environment of the membrane vesicle; concomitant with this alteration in receptor affinity, receptor selectivity for the structure of the native hormone decreases 1.5- to 40-fold in hepatocyte-derived vesicles. Consideration of receptor affinity in relation to receptor number suggests that hepatocyte glucagon binding is distributed about equally between high and low affinity receptor populations at typical portal hormone levels. Nevertheless, consideration of receptor binding in relation to biological activity suggests that the activity of glucagon in inhibiting carbohydrate flux into glycogen is attributable to occupancy of the high affinity receptor population. 相似文献
9.
10.