全文获取类型
收费全文 | 398篇 |
免费 | 32篇 |
专业分类
430篇 |
出版年
2021年 | 6篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2016年 | 3篇 |
2015年 | 14篇 |
2014年 | 8篇 |
2013年 | 18篇 |
2012年 | 25篇 |
2011年 | 20篇 |
2010年 | 7篇 |
2009年 | 6篇 |
2008年 | 8篇 |
2007年 | 14篇 |
2006年 | 10篇 |
2005年 | 10篇 |
2004年 | 12篇 |
2003年 | 8篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 10篇 |
1999年 | 14篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1976年 | 8篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 8篇 |
1970年 | 7篇 |
1961年 | 3篇 |
1958年 | 5篇 |
1956年 | 4篇 |
1946年 | 2篇 |
排序方式: 共有430条查询结果,搜索用时 15 毫秒
101.
Summary Wild-type strains of Aspergillus niger were transformed with integrative vectors. The number of stable transformants varied from approximately 20–30/g up to 17,000/g using acetamide and hygromycin B selection, respectively. The introduction of deletions of 5 and 3 non-coding regions of the acetamidase gene (amdS+) revealed that these sequences influenced the number of transformants. The molecular characterization of A. niger transformants revealed that several copies of the vectors were tandemly integrated into the nuclear DNA. These oligomers were stably inherited, even after 100 days of growth on non-selective medium. The expression of the vector-encoded genes was confirmed by evidence from the mRNAs and corresponding proteins encoded by the selectable marker genes.
Offprint requests to: K. Esser 相似文献
102.
White J Lukacik P Esser D Steward M Giddings N Bright JR Fritchley SJ Morgan BP Lea SM Smith GP Smith RA 《Protein science : a publication of the Protein Society》2004,13(9):2406-2415
Decay-accelerating factor (DAF, CD55) is a glycophosphatidyl inositol-anchored glycoprotein that regulates the activity of C3 and C5 convertases. In addition to understanding the mechanism of complement inhibition by DAF through structural studies, there is also an interest in the possible therapeutic potential of the molecule. In this report we describe the cloning, expression in Escherichia coli, isolation and membrane-targeting modification of the four short consensus repeat domains of soluble human DAF with an additional C-terminal cysteine residue to permit site-specific modification. The purified refolded recombinant protein was active against both classical and alternative pathway assays of complement activation and had similar biological activity to soluble human DAF expressed in Pichia pastoris. Modification with a membrane-localizing peptide restored cell binding and gave a large increase in antihemolytic potency. These data suggested that the recombinant DAF was correctly folded and suitable for structural studies as well as being the basis for a DAF-derived therapeutic. Crystals of the E. coli-derived protein were obtained and diffracted to 2.2 A, thus permitting the first detailed X-ray crystallography studies on a functionally active human complement regulator protein with direct therapeutic potential. 相似文献
103.
J W Shiver J R Dankert J J Donovan A F Esser 《The Journal of biological chemistry》1986,261(21):9629-9636
The domain structure of human complement protein C9 was investigated by determining the functional activities of the NH2-terminal (C9a) and COOH-terminal (C9b) fragments obtained by cleavage of C9 with alpha-thrombin. The two fragments were separated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renatured by dialysis against buffers containing zwitterionic detergents. The C9b fragment produced membranolytic activities in three independent assays. First, it produced single, ion-conducting channels of varying conductances in planar lipid membranes. Most of the channels had an average conductance of 11 picoSiemens and an average lifetime of about 30 s. The channels showed lipid specificity and a 3-fold preference for conducting K+ over Na+. Second, the fragment also caused specific marker release from liposomes which was inhibitable by a C9b-specific monoclonal antibody, and third, it lysed erythrocytes in the absence of a fully assembled C5b-8 complex. The isolated C9a fragment did not produce single channels in planar lipid membranes but was also effective in releasing markers from liposomes and in lysing erythrocytes. Secondary structure predictions indicate the presence of several amphiphilic, "surface-seeking" segments in the primary structure of C9 which are mainly alpha-helices in C9b and beta-sheets in C9a. These results may indicate the presence of surface-binding domains in the NH2-terminal half and channel-forming domains in the COOH-terminal portion of native, monomeric C9. 相似文献
104.
105.
106.
Andrew MF Liu Rico KH Lo Emily X Guo Maurice KC Ho Richard D Ye Yung H Wong 《BMC structural biology》2011,11(1):17
Background
G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bind a multitude of effectors and regulatory proteins. Yet it remains unclear if the different proteins utilize distinct or common structural motifs on the Gα subunit for binding. Using Gα16 as a model, we asked if its recently discovered adaptor protein tetratricopeptide repeat 1 (TPR1) binds to the same region as its canonical effector, phospholipase Cβ (PLCβ). 相似文献107.
Ubiquinol cytochrome c oxido-reductase (EC. 1.10.2.2, bc1) is an integral membrane protein complex essential to cellular respiration. Structures of the 11-subunit mitochondrial bc1 complex were determined with and without the fungicide famoxadone. Specific inhibition by famoxadone is achieved through a coordinated optimization of aromatic-aromatic interactions where conformational rearrangements in famoxadone and in residues lining the inhibitor-binding pocket produce a network of aromatic-aromatic interactions that mimic the crystal lattice of benzene. The profound aromatic-aromatic interactions as supported by prior mutagenesis provide a structural basis for specific protein-ligand interaction in a hydrophobic environment. Dramatic conformational changes, both in cyt. b and ISP subunits in the inhibitor-protein complex, confer experimental evidence for a functional role of cytochrome b in the induced conformational arrest of ISP and allow the identification of a possible intrasubunit signal transduction pathway that controls the movement of ISP. These results support an inhibitory mechanism that is consistent with the requirement for ISP movement in the electron transfer of this complex. 相似文献
108.
Inactivation of Human Immunodeficiency Virus Type 1 Infectivity with Preservation of Conformational and Functional Integrity of Virion Surface Proteins 总被引:18,自引:9,他引:18 下载免费PDF全文
109.
110.
The physical state of membrane lipids modulates the activation of the first component of complement.
A F Esser R M Bartholomew J W Parce H M McConnell 《The Journal of biological chemistry》1979,254(6):1768-1770
Activation of the first component of human complement (C1) by bilayer-embedded nitroxide spin label lipid haptens and specific rabbit antinitroxide antibody has been measured. The nitroxide spin label hapten was contained in host bilayers of either dimyristoyl phosphatidylcholine or dipalmitoyl phosphatidylcholine in the form of both liposomes and vesicles. At a temperature of 32 degrees C, which is intermediate between the hydrocarbon chain-melting temperatures of the two phospholipids, activation of C1 in such vesicles and liposomes is more efficient in the fluid membrane. Studies of C1 activation in binary mixtures of cholesterol and dipalmitoyl phosphatidylcholine indicate that the activation of C1 is not limited by the lateral diffusion of the lipid haptens in these membranes. 相似文献