全文获取类型
收费全文 | 647篇 |
免费 | 33篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 21篇 |
2013年 | 23篇 |
2012年 | 42篇 |
2011年 | 49篇 |
2010年 | 29篇 |
2009年 | 27篇 |
2008年 | 28篇 |
2007年 | 33篇 |
2006年 | 32篇 |
2005年 | 35篇 |
2004年 | 32篇 |
2003年 | 31篇 |
2002年 | 30篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 16篇 |
1997年 | 13篇 |
1996年 | 12篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 12篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1986年 | 9篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1976年 | 2篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1967年 | 3篇 |
1963年 | 2篇 |
1955年 | 2篇 |
排序方式: 共有680条查询结果,搜索用时 15 毫秒
31.
Lipid Segregation and Membrane Budding Induced by the Peripheral Membrane Binding Protein Annexin A2
Patrick Drücker Milena Pejic Hans-Joachim Galla Volker Gerke 《The Journal of biological chemistry》2013,288(34):24764-24776
The formation of dynamic membrane microdomains is an important phenomenon in many signal transduction and membrane trafficking events. It is driven by intrinsic properties of membrane lipids and integral as well as membrane-associated proteins. Here we analyzed the ability of one peripherally associated membrane protein, annexin A2 (AnxA2), to induce the formation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-rich domains in giant unilamellar vesicles (GUVs) of complex lipid composition. AnxA2 is a cytosolic protein that can bind PI(4,5)P2 and other acidic phospholipids in a Ca2+-dependent manner and that has been implicated in cellular membrane dynamics in endocytosis and exocytosis. We show that AnxA2 binding to GUVs induces lipid phase separation and the recruitment of PI(4,5)P2, cholesterol and glycosphingolipids into larger clusters. This property is observed for the full-length monomeric protein, a mutant derivative comprising the C-terminal protein core domain and for AnxA2 residing in a heterotetrameric complex with its intracellular binding partner S100A10. All AnxA2 derivatives inducing PI(4,5)P2 clustering are also capable of forming interconnections between PI(4,5)P2-rich microdomains of adjacent GUVs. Furthermore, they can induce membrane indentations rich in PI(4,5)P2 and inward budding of these membrane domains into the lumen of GUVs. This inward vesiculation is specific for AnxA2 and not shared with other PI(4,5)P2-binding proteins such as the pleckstrin homology (PH) domain of phospholipase Cδ1. Together our results indicate that annexins such as AnxA2 can efficiently induce membrane deformations after lipid segregation, a mechanism possibly underlying annexin functions in membrane trafficking. 相似文献
32.
EDTA-induced Membrane Fluidization and Destabilization: Biophysical Studies on Artificial Lipid Membranes 总被引:5,自引:0,他引:5
Prachayasittikul V Isarankura-Na-Ayudhya C Tantimongcolwat T Nantasenamat C Galla HJ 《Acta biochimica et biophysica Sinica》2007,39(11):901-913
The molecular mechanism of ethylenediaminetetraacetic acid (EDTA)-induced membrane destabilization has been studied using a combination of four biophysical techniques on artificial lipid membranes. Data from Langmuir film balance and epifluorescence microscopy revealed the fluidization and expansion effect of EDTA on phase behavior of monolayers of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or mixtures of DPPC and metal-chelating lipids, such as N^a,N^a-Bis[carboxymethyl]-N^ε [(dioctadecylamino)succinyl]-L-lysine or 1,2-dioleoyl-sn-glycero-3-[N-(5-amino- 1 -carboxypentyl iminodiacetic acid) succinyl]. A plausible explanation could be drawn from the electrostatic interaction between negatively charged groups of EDTA and the positively charged choline head group of DPPC. Intercalation of EDTA into the lipid membrane induced membrane curvature as elucidated by atomic force microscopy. Growth in size and shape of the membrane protrusion was found to be time-dependent upon exposure to EDTA. Further loss of material from the lipid membrane surface was monitored in real time using a quartz crystal microbalance. This indicates membrane restabilization by exclusion of the protrusions from the surface. Loss of lipid components facilitates membrane instability, leading to membrane permeabilization and lysis. 相似文献
33.
Hoppen J Dietz M Warsow G Rohde R Schüller HJ 《Molecular genetics and genomics : MGG》2007,278(3):317-330
34.
Hans-Joachim Gregor 《Feddes Repertorium》1982,93(5):351-362
In contrast to the opinion of Miki (1952 b, p. 349) the genus Hemitrapa Miki (Trapellaceae) is not only found in Asia and America but also in Europe. Wrongly determined fossils of the type „Trapa silesiaca Goeppert”︁ (the original species from Schoßnitz in Poland is under research by M. Lancucka-Srodoniowa, Krakow) belong to the genus Hemitrapa Miki. Some other Bavarian fossils are newly decribed here as Hemitrapa heissigii sp. nov. Hemitrapa fossils grew not only in the Senftenberg area (Menzel 1906), in Silesia (Kräusel 1920) or the Niederlausitz area (Menzel in Gothan & Sapper 1933), at Konin (Raniecka-Bobrowska 1954), but possibly also near Cologne (Kilpper 1969 and Kramer 1974) and at Ponholz (Gregor 1980). Especially in the Middle Miocene Upper Freshwater Molasse of Bavaria the fossil species Hemitrapa heissigii is found in numerous specimens near Eberstetten, Haag a. d. Amper and Rauscheröd (all in southern Bavaria). Hemitrapa heissigii can be used as an index-fossil and signs Uppermost Miocene sediments (Badenian, Samartian). The occurence in Pliocene localities is to be prooved. The whole group around Hemitrapa is considered to be a “late element” (Upper Miocene) in Europe. 相似文献
35.
Abstract A sulfanilic acid (4-aminobenzenesulfonic acid) degrading culture consisting of two strains (strain S1 and S2), was studied. Only strain S1 was able to attack sulfanilic acid. When strain S1 was cultavated in a mineral medium with sulfanilic acid an intensive violet colour was observed. The accumulating metabolite was isolated from the culture supernatant. By comparison with an authentic compound the metabolite was identified as catechol-4-sulfonic acid by thin layer and high performance liquid chromatography and by UV- and H-NMR spectroscopy. The occurrence of catechol-4-sulfonic acid indicates that there is no release of the sulfonic group before ring cleavage. 相似文献
36.
Elongation factor Tu (EF-Tu) undergoes a large conformational transition when switching from the GTP to GDP forms. Structural changes in the switch I and II regions in the G domain are particularly important for this rearrangement. In the switch II region, helix alpha2 is flanked by two glycine residues: Gly(83) in the consensus element DXXG at the N terminus and Gly(94) at the C terminus. The role of helix alpha2 was studied by pre-steady-state kinetic experiments using Escherichia coli EF-Tu mutants where either Gly(83), Gly(94), or both were replaced with alanine. The G83A mutation slows down the association of the ternary complex EF-Tu.GTP.aminoacyl-tRNA with the ribosome and abolishes the ribosome-induced GTPase activity of EF-Tu. The G94A mutation strongly impairs the conformational change of EF-Tu from the GTP- to the GDP-bound form and decelerates the dissociation of EF-Tu.GDP from the ribosome. The behavior of the double mutant is dominated by the G83A mutation. The results directly relate structural transitions in the switch II region to specific functions of EF-Tu on the ribosome. 相似文献
37.
Elongation factor (EF) Tu alternates between two interaction partners, EF-Ts and the ribosome, during its functional cycle.
On the ribosome, the interaction involves, among others, ribosomal protein L7/12. Here we compare EF-Ts and L7/12 with respect
to the conservation of sequence and structure. There is significant conservation of functionally important residues in the
N-terminal domain of EF-Ts and in the C-terminal domain of L7/12. The structure alignment based on the crystal structures
of the two domains suggests a high degree of similarity between the αA–βD–αB motif in L7/12 and the h1–turn–h2 motif in EF-Ts
which defines a common structural motif. The motif is remarkably similar with respect to fold, bulkiness, and charge distribution
of the solution surface, suggesting that it has a common function in binding EF-Tu.
Received: 12 June 2000 / Accepted: 10 October 2000 相似文献
38.
Measurement of transendothelial or transepithelial electrical resistances (TERs) is a straightforward in situ experimental approach to monitor the expression or modulation of barrier-forming cell-to-cell contacts (tight junctions) in cultured cells grown on porous filters. Although widely accepted, there is currently no device available to automatically measure the time course of TERs under ordinary cell culture conditions (37 degrees C, 5% or 10% CO2). This paper describes a development from our laboratory that is capable of following in parallel the TERs of several filter-grown cell layers with time and in an entirely computer-controlled fashion. The cell cultures can be followed even in long-term experiments without any manual assistance or opening of the incubator Besides reading TER values, this approach also returns the electrical capacitance of the cell layers, which is indicative of the expression of microvilli and other membrane extrusions. The device is based on reading the frequencydependent impedance of the cell layer, followed by equivalent circuit modeling to extract the cell-related parameters. It is compatible with several multi-well formats (up to 96 wells) and controlled by custom-designed software that reads, analyzes, and presents the data. 相似文献
39.
Anti-angiogenic effects of thalidomide: expression of apoptosis-inducible active-caspase-3 in a three-dimensional collagen gel culture of aorta 总被引:2,自引:2,他引:0
The anti-angiogenic properties of thalidomide have led to the use of the agent as a remedy for multiple myeloma. Nevertheless, the anti-angiogenic moiety of thalidomide remains unidentified. In this study we examined the anti-angiogenic effects of thalidomide in an in vitro model using a three-dimensional collagen gel culture. Angiogenesis was significantly inhibited when the culture was treated with thalidomide plus cytochrome P-450 (CYP2B4), and the migrating cells and tubules were positive for active-caspase-3 in an accompanying immunohistochemical investigation. Transmission electron microscopic observation also confirmed that active-caspase-3-positive cells demonstrated apoptotic characteristics. This study is the first to morphologically demonstrate the effect of thalidomide in directly inducing the apoptosis of new tubules and migrating cells on a three-dimensional collagen gel culture of aorta. Taken together with earlier findings, our new results indicate that the thalidomide-induced inhibition of angiogenesis involves apoptosis in addition to the suppression of TNF- and inhibition of cell migration from aorta explants, i.e., the factors important for capillarogenesis. 相似文献
40.
Isarankura Na Ayudhya C Prachayasittikul V Galla HJ 《European biophysics journal : EBJ》2004,33(6):522-534
Membrane-based bioanalytical devices for metal determination using green fluorescent protein as the sensor molecule may be a useful future biomimetic material. However, in order to develop such a device, it is necessary first to understand the interaction of the protein with lipid membranes. Thus we have investigated the interaction between chimeric cadmium-binding green fluorescent proteins (CdBPGFPs) and lipid monolayers, using a film-balance technique complemented with epifluorescence microscopy. The binding avidity was monitored from the surface pressure vs. area isotherms or from the measured increase in the lateral pressure upon injection of the chimeric CdBPGFPs beneath the lipid monolayer. Increased fluidization as well as expansion of the surface area were shown to depend on the concentration of the CdBPGFPs. The kinetics of the protein-induced increase in lateral pressure was found to be biphasic. The chimeric CdBPGFPs possessed high affinity to the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer with a dissociation constant of Kd=10–8M. Epifluorescence measurements showed that this affinity is due to the presence of the Cd-binding peptide, which caused the GFP to incorporate preferentially to the liquid phase and defect part of the rigid domain at low interfacial pressure. At high compression, the Cd-binding peptide could neither incorporate nor remain in the lipid core. However, specific orientation of the chimeric CdBPGFPs underneath the air–water interface was achieved, even under high surface pressure, when the proteins were applied to the metal-chelating lipid-containing surfaces. This specific binding could be controlled reversibly by the addition of metal ions or metal chelator. The reversible binding of the chimeric CdBPGFPs to metal-chelating lipids provided a potential approach for immobilization, orientation and lateral organization of a protein at the membrane interface. Furthermore, the feasibility of applying the chelator lipids for the codetermination of metal ions with specific ligands was also revealed. Our finding clearly demonstrates that a strong interaction, particularly with fluid lipid domains, could potentially be used for sensor development in the future.Abbreviations GFP green fluorescent protein - CdBPGFPs cadmium-binding green fluorescent protein - DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine - AAS atomic absorption spectrometry - Cd2+ cadmium (II) - Zn2+ zinc (II) - Cu2+ copper (II) - Ni2+ nickel (II) - E. coli Escherichia coli - NTA-DOGS 1,2-dioleoyl-sn-glycero-3-(N-(5-amino-1-carboxypentyl iminodiacetic acid) succinyl) - His6GFP hexahistidine green fluorescent protein - CdBP4GFP four-repeat cadmium-binding peptide green fluorescent protein - His6CdBP4GFP hexahistidine four-repeat cadmium-binding peptide green fluorescent protein - IMAC immobilized-metal-affinity chromatography - PBS phosphate-buffered saline - mN/m millinewton per metre - le liquid expanded - lc liquid condensed - PE phosphatidyl ethanolamine - PI phosphatidyl inositol - NTA nitrilotriacetic acid - EDTA ethylenediamine tetraacetic acid - RESA ring-infected erythrocyte surface antigen - CdBP cadmium-binding peptide 相似文献