全文获取类型
收费全文 | 709篇 |
免费 | 83篇 |
专业分类
792篇 |
出版年
2018年 | 6篇 |
2016年 | 6篇 |
2015年 | 15篇 |
2014年 | 12篇 |
2013年 | 16篇 |
2012年 | 26篇 |
2011年 | 11篇 |
2010年 | 13篇 |
2009年 | 10篇 |
2008年 | 18篇 |
2007年 | 29篇 |
2006年 | 21篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 14篇 |
2002年 | 20篇 |
2001年 | 20篇 |
2000年 | 14篇 |
1999年 | 20篇 |
1998年 | 8篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1993年 | 14篇 |
1992年 | 16篇 |
1991年 | 17篇 |
1990年 | 19篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 24篇 |
1985年 | 14篇 |
1984年 | 17篇 |
1983年 | 15篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 14篇 |
1979年 | 14篇 |
1978年 | 14篇 |
1977年 | 18篇 |
1976年 | 17篇 |
1975年 | 16篇 |
1974年 | 23篇 |
1973年 | 6篇 |
1972年 | 17篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1969年 | 8篇 |
1968年 | 6篇 |
1967年 | 7篇 |
1966年 | 6篇 |
排序方式: 共有792条查询结果,搜索用时 15 毫秒
71.
WW domain sequence activity relationships identified using ligand recognition propensities of 42 WW domains 下载免费PDF全文
Otte L Wiedemann U Schlegel B Pires JR Beyermann M Schmieder P Krause G Volkmer-Engert R Schneider-Mergener J Oschkinat H 《Protein science : a publication of the Protein Society》2003,12(3):491-500
WW domains mediate protein-protein interactions in a number of different cellular functions by recognizing proline-containing peptide sequences. We determined peptide recognition propensities for 42 WW domains using NMR spectroscopy and peptide library screens. As potential ligands, we studied both model peptides and peptides based on naturally occurring sequences, including phosphorylated residues. Thirty-two WW domains were classified into six groups according to detected ligand recognition preferences for binding the motifs PPx(Y/poY), (p/phi)P(p,g)PPpR, (p/phi)PPRgpPp, PPLPp, (p/xi)PPPPP, and (poS/poT)P (motifs according to modified Seefeld Convention 2001). In addition to these distinct binding motifs, group-specific WW domain consensus sequences were identified. For PPxY-recognizing domains, phospho-tyrosine binding was also observed. Based on the sequences of the PPx(Y/poY)-specific group, a profile hidden Markov model was calculated and used to predict PPx(Y/poY)-recognition activity for WW domains, which were not assayed. PPx(Y/poY)-binding was found to be a common property of NEDD4-like ubiquitin ligases. 相似文献
72.
Sultana R Fuchs R Schmickler H Schlegel K Budzikiewicz H Siddiqui BS Geoffrey V Meyer JM 《Zeitschrift für Naturforschung. C, Journal of biosciences》2000,55(11-12):857-865
From Pseudomonas sp. CFML 95-275 a pyoverdin was isolated with a cyclopeptidic substructure. It could be shown that this pyoverdin is identical with one obtained from Pseudomonas fluorescens BTP 7 for which a lactone structure had been deduced from the interpretation of a FAB spectrum. The elucidation of the correct structure of the pyoverdin is described. 相似文献
73.
Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes 总被引:1,自引:0,他引:1
Cells generally maintain an asymmetric distribution of phospholipids across the plasma membrane bilayer, restricting the phospholipid, phosphatidylserine (PS), to the inner leaflet of the plasma membrane. When cells undergo apoptosis, this asymmetric transbilayer distribution is lost, bringing PS to the surface where it acts as a signal for engulfment by phagocytes. The fluorescent dye merocyanine 540 specifically stains the plasma membrane of apoptotic cells which have lost their asymmetric distribution of phospholipids. However, it also stains non-apoptotic macrophages, suggesting that phospholipid asymmetry may not be maintained in these cells, and thus that they may express PS on their surface. Here, the PS-binding protein, annexin V, was used to show that in fact normal macrophages do express PS on their surface. Furthermore, pre-treating macrophages with annexin V was found to inhibit phagocytosis of apoptotic thymocytes and thymocytes on which PS expression was artificially induced, but did not inhibit phagocytosis of latex beads or Fc receptor-mediated phagocytosis of opsonized erythrocytes. These results indicate that PS is constitutively expressed on the surface of macrophages and is functionally significant for the phagocytosis of PS-expressing target cells. 相似文献
74.
Suprynowicz FA Sparkowski J Baege A Schlegel R 《The Journal of biological chemistry》2000,275(7):5111-5119
The E5 oncoprotein of bovine papillomavirus type 1 is a Golgi-resident, 44-amino acid polypeptide that can transform fibroblast cell lines by activating endogenous platelet-derived growth factor receptor beta (PDGF-R). However, the recent discovery of E5 mutants that exhibit strong transforming activity but minimal PDGF-R tyrosine phosphorylation indicates that E5 can potentially use additional signal transduction pathway(s) to transform cells. We now show that two classes of E5 mutants, despite poorly activating the PDGF-R, induce tyrosine phosphorylation and activation of phosphoinositide 3-kinase (PI 3-K) and that this activation is resistant to a selective inhibitor of PDGF-R kinase activity, tyrphostin AG1296. Consistent with this independence from PDGF-R signaling, the E5 mutants fail to induce significant cell proliferation in the absence of PDGF, unlike wild-type E5 or the sis oncoprotein. Despite differences in growth factor requirements, however, both wild-type E5 and mutant E5 cell lines form colonies in agarose. Interestingly, activation of PI 3-K occurs without concomitant activation of the ras-dependent mitogen-activated protein kinase pathway. The known ability of constitutively activated PI 3-K to induce anchorage-independent cell proliferation suggests a mechanism by which the mutant E5 proteins transform cells. 相似文献
75.
Caveolins form interlocking networks on the cytoplasmic face of caveolae. The cytoplasmically directed N and C termini of caveolins are separated by a central hydrophobic segment, which is believed to form a hairpin within the membrane. Here, we report that the caveolin scaffolding domain (CSD, residues 82-101), and the C terminus (residues 135-178) of caveolin-1 are each sufficient to anchor green fluorescent protein (GFP) to membranes in vivo. We also show that the first 16 residues of the C terminus (i.e. residues 135-150) are necessary and sufficient to attach GFP to membranes. When fused to the caveolin-1 C terminus, GFP co-localizes with two trans-Golgi markers and is excluded from caveolae. In contrast, the CSD targets GFP to caveolae, albeit less efficiently than full-length caveolin-1. Thus, caveolin-1 contains at least two membrane attachment signals: the CSD, dictating caveolar localization, and the C terminus, driving trans-Golgi localization. Additionally, we find that caveolin-1 oligomer/oligomer interactions require the distal third of the caveolin-1 C terminus. Thus, the caveolin-1 C-terminal domain has two separate functions: (i) membrane attachment (proximal third) and (ii) protein/protein interactions (distal third). 相似文献
76.
The histones H4 are known as highly conserved proteins. However, in ciliates a high degree of variation was found compared
both to other eukaryotes and between the ciliate species. To date, only H4 histones of species belonging to two distantly
related classes have been investigated. In order to obtain more detailed information on histone H4 variation in ciliates we
undertook a comprehensive sequence analysis of PCR-amplified internal H4 fragments from 12 species belonging to seven out
of the nine currently recognized ciliate classes. In addition, we used PCR primers to amplify longer fragments of H3 and H4
genes including the intergenic region.
The encoded amino acid sequences reveal a high number of differences when compared with those of other eukaryotes and the
ciliate species investigated. Furthermore, in some species H4 gene variants were detected, which result in amino acid differences.
The greatest number of substitutions and insertions found was in the amino terminal region of the H4 histones. However, all
sequences possess a conserved region corresponding to those of all other eukaryotic H4 histones.
The histone gene variations were used to reconstruct phylogenetic relationships. The tree from our data matches perfectly
with the ribosomal RNA data: The heterotrichs, which were considered as a late branching lineage, diverge at the base of the
ciliate tree and groups formerly thought to represent ancestral lineages now appear as highly derived ciliates.
Received: 4 April 1997 / Accepted: 1 August 1997 相似文献
77.
W. Schlegel Laurence M. Demers Helga E. Hilldebrandt-Stark Harold R. Behrman Roy O. Greep 《Prostaglandins & other lipid mediators》1974,5(5)
The enzyme system, 15-hydroxyprostaglandin dehydrogenase, which catalyzes the first inactivation step in the catabolism of the prostaglandins has been isolated and purified 107-fold from human placenta. Kinetic studies reveal different Michaelis-Menten constants for most of the naturally occurring prostaglandins. The Km for PGE2 was found to be 10 μM, for PGE1, 27 μM; for PGA2, 32 μM; for PGA1, 33 μM; and for PGF2α 59 μM. The enzyme has a sharp pH-optimum between 7.5 and 8.8. Prostaglandin dehydrogenase appears to be isoenzymic as judged by separation on polyacrylamide disc gel electrophoresis. Inhibition studies with the partially purified enzyme indicate that progesterone and estrogen may influence the conversion of biologically active prostaglandins into the biologically inactive 15-ketoprostaglandins. These findings offer evidence for the control of prostaglandin metabolism in the human placenta. 相似文献
78.
Manuel Huster Christine Müller‐Renno Christiane Ziegler Christin Schlegel Roland Ulber Kai Muffler 《Engineering in Life Science》2016,16(1):88-92
Chloroperoxidase (CPO) is a versatile enzyme, which is secreted by the marine fungus Caldariomyces fumago (Leptoxyphium fumago). However, the application of the enzyme is hampered by its high price, which is due to the costly, labor‐intensive purification process. One challenge of the downstream process is the removal of a coproduced black pigment that forms a complex with the active enzyme. While strain development can be considered as an option to reduce the synthesis of the interfering pigment, the metabolism of the microorganism can be altered alternatively by using the biofilm growth mode of the fungus. The aim of this study was to reduce pigment formation during CPO synthesis. We investigated for the first time CPO production during C. fumago biofilm growth initiated through the presence of different microstructured stainless steel surfaces (material number: 1.4571; AISI 316Ti). CPO production by C. fumago was similar when grown as a biofilm or in suspension, whereas pigment formation was drastically reduced by cells grown on moderately structured surfaces (Ra = 0.13 ± 0.02 μm). The possibilities of biofilm growth for changing cell properties and for continuous fermentation are discussed. 相似文献
79.
The transbilayer distribution of phospholipids in right-side-out and inside-out vesicles derived from human erythrocytes was studied by phospholipase A2 digestion assays and by staining with the fluorescent dye merocyanine 540. In both types of vesicles, the normal asymmetric distribution of phospholipids characteristic of intact cells was disrupted. Because both types of vesicles are deficient in spectrin, the major protein of the cytoskeletal network which normally underlies the membrane, these results support the contention that spectrin is involved in the maintenance of phospholipid asymmetry. 相似文献
80.