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排序方式: 共有118条查询结果,搜索用时 203 毫秒
1.
Algirdas Mikalkėnas Bazilė Ravoitytė Daiva Tauraitė Elena Servienė Rolandas Meškys 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):384-389
Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors. 相似文献
2.
The present study on saponin-treated rat heart muscle fibers has revealed a new function of the fatty acid oxidation system in the regulation of the outer mitochondrial membrane (OMM) permeability for ADP. It is found that oxidation of palmitoyl-CoA+carnitine, palmitoyl-L-carnitine and octanoyl-L-carnitine (alone or in combination with pyruvate+malate) dramatically decreased a very high value of apparent K(m) of oxidative phosphorylation for ADP. Octanoyl-D-carnitine, as well as palmitate, palmitoyl-CoA, and palmitoyl-L-carnitine were not effective in this respect, when their oxidation was prevented by the absence of necessary cofactors or blocked with rotenone. Our data suggest that oxidation, but not transport of fatty acids into mitochondria, induces an increase in the OMM permeability for ADP. 相似文献
3.
Norkus E Prusinskas K Vaskelis A Jaciauskiene J Stalnioniene I Macalady DL 《Carbohydrate research》2007,342(1):71-78
Saccharose, forming sufficiently stable complexes with copper(II) ions in alkaline solutions, was found to be a suitable ligand for copper(II) chelating in alkaline (pH>12) electroless copper deposition solutions. Reduction of copper(II)-saccharose complexes by hydrated formaldehyde was investigated and the copper deposits formed were characterized. The thickness of the compact copper coatings obtained under optimal operating conditions in 1h reaches ca. 2 microm at ambient temperature. The plating solutions were stable and no signs of Cu(II) reduction in the bulk solution were observed. Results were compared with those systems operating with other copper(II) ligands. 相似文献
4.
Augustaitis A Augustaitiene I Cinga G Mazeika J Deltuvas R Juknys R Vitas A 《TheScientificWorldJournal》2007,7(Z1):58-66
This study aimed to explore if changes in stem increment of Scots pines (Pinus sylvestris L.) could be related to changes in ambient ozone concentration when the impact of tree dendrometric parameters (age, diameter) and crown defoliation are accounted for. More than 200 dominant and codominant trees from 12 pine stands, for which crown defoliation had been assessed since 1994, were chosen for increment boring and basal area increment computing. Stands are located in Lithuanian national parks, where since 1994-95 Integrated Monitoring Stations have been operating. Findings of the study provide statistical evidence that peak concentrations of ambient ozone (O3) can have a negative impact on pine tree stem growth under field conditions where O3 exposure is below phytotoxic levels. 相似文献
5.
Solution NMR spectroscopy is an extremely powerful technology for the study of biomolecular dynamics and site-specific molecular interactions. An important limitation in the past has been molecule size, with molecular weights of targets seldom exceeding 50 kDa. New labeling technology and NMR experiments are changing this paradigm so that applications for investigating supramolecular complexes are starting to become feasible. Here we describe a strategy developed in our laboratory that involves the use of labeled methyl groups of isoleucine, leucine and valine residues in proteins as probes, along with experiments that significantly enhance the lifetimes of the resulting signals. We describe the application of these methods to a number of systems with molecular weights in the hundreds of kilodaltons. 相似文献
6.
Burritt JB Foubert TR Baniulis D Lord CI Taylor RM Mills JS Baughan TD Roos D Parkos CA Jesaitis AJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):6082-6089
mAb NL7 was raised against purified flavocytochrome b(558), important in host defense and inflammation. NL7 recognized the gp91(phox) flavocytochrome b(558) subunit by immunoblot and bound to permeabilized neutrophils and neutrophil membranes. Epitope mapping by phage display analysis indicated that NL7 binds the (498)EKDVITGLK(506) region of gp91(phox). In a cell-free assay, NL7 inhibited in vitro activation of the NADPH oxidase in a concentration-dependent manner, and had marginal effects on the oxidase substrate Michaelis constant (K(m)). mAb NL7 did not inhibit translocation of p47(phox), p67(phox), or Rac to the plasma membrane, and bound its epitope on gp91(phox) independently of cytosolic factor translocation. However, after assembly of the NADPH oxidase complex, mAb NL7 bound the epitope but did not inhibit the generation of superoxide. Three-dimensional modeling of the C-terminal domain of gp91(phox) on a corn nitrate reductase template suggests close proximity of the NL7 epitope to the proposed NADPH binding site, but significant separation from the proposed p47(phox) binding sites. We conclude that the (498)EKDVITGLK(506) segment resides on the cytosolic surface of gp91(phox) and represents a region important for oxidase function, but not substrate or cytosolic component binding. 相似文献
7.
Girniene J Tatibouët A Sackus A Yang J Holman GD Rollin P 《Carbohydrate research》2003,338(8):711-719
The glucose transporter 5 (GLUT5)-a specific D-fructose transporter-belongs to a family of facilitating sugar transporters recently enlarged by the human genome sequencing. Prompted by the need to develop specific photolabels of these isoforms, we have studied the interaction of conformationally locked D-fructose and L-sorbose derived 1,3-oxazolidin-2-thiones and 1,3-oxazolidin-2-ones to provide a rational basis for an interaction model. The inhibition properties of the D-fructose transporter GLUT5 by glyco-1,3-oxazolidin-2-thiones and glyco-1,3-oxazolidin-2-ones is now reported. In vitro, the fused-rings systems tested showed an efficient inhibition of GLUT5, thus bringing new insights on the interaction of D-fructose with GLUT5. 相似文献
8.
Kopustinskiene DM Jovaisiene J Liobikas J Toleikis A 《Journal of bioenergetics and biomembranes》2002,34(1):49-53
We investigated the effects of KATP channel openers diazoxide and pinacidil on the respiration rate and membrane potential () of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8–1348.3 M) increased the V
2 (-ADP) respiration rate accordingly by 13–208% and 30–273% and decreased the by 2–17% and 6–55%. These effects were also similar in the respiration medium without K+. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process. 相似文献
9.
Anionic amphiphiles such as sodium- and lithium dodecyl sulfate (SDS, LDS), or arachidonate (AA) initiate NADPH oxidase and proton channel activation in cell-free systems and intact neutrophils. To investigate whether these amphiphiles exert allosteric effects on cytochrome b, trisulfopyrenyl-labeled wheat germ agglutinin (Cascade Blue-wheat germ agglutinin, CCB-WGA) was used as an extrinsic fluorescence donor for resonance energy transfer (RET) to the intrinsic heme acceptors of detergent-solubilized cytochrome b. In solution, cytochrome b complexed with the CCB-WGA causing a rapid, saturable, carbohydrate-dependent quenching of up to approximately 55% of the steady-state fluorescence. Subsequent additions of SDS, LDS, or AA to typical cell-free oxidase assay concentrations completely relaxed the fluorescence quenching. The relaxation effects were specific, and not caused by dissociation of the CCB-WGA-cytochrome b complex or alterations in the spectral properties of the chromophores. In contrast, addition of the oxidase antagonist, arachidonate methyl ester, caused an opposite effect and was able to partially reverse the activator-induced relaxation. We conclude that the activators induce a cytochrome b conformation wherein the proximity or orientation between the hemes and the extrinsic CCB fluorescence donors has undergone a significant change. These events may be linked to NADPH oxidase assembly and activation or proton channel induction. 相似文献
10.
Brendan M Mumey Brian W Bailey Bonnie Kirkpatrick Algirdas J Jesaitis Thomas Angel Edward A Dratz 《Journal of computational biology》2003,10(3-4):555-567
Antibodies that bind to protein surfaces of interest can be used to report the three-dimensional structure of the protein as follows: Proteins are composed of linear polypeptide chains that fold together in complex spatial patterns to create the native protein structure. These folded structures form binding sites for antibodies. Antibody binding sites are typically "assembled" on the protein surface from segments that are far apart in the primary amino acid sequence of the target proteins. Short amino acid probe sequences that bind to the active region of each antibody can be used as witnesses to the antibody epitope surface and these probes can be efficiently selected from random sequence peptide libraries. This paper presents a new method to align these antibody epitopes to discontinuous regions of the one-dimensional amino acid sequence of a target protein. Such alignments of the epitopes indicate how segments of the protein sequence must be folded together in space and thus provide long-range constraints for solving the 3-D protein structure. This new antibody-based approach is applicable to the large fraction of proteins that are refractory to current approaches for structure determination and has the additional advantage of requiring very small amounts of the target protein. The binding site of an antibody is a surface, not just a continuous linear sequence, so the epitope mapping alignment problem is outside the scope of classical string alignment algorithms, such as Smith-Waterman. We formalize the alignment problem that is at the heart of this new approach, prove that the epitope mapping alignment problem is NP-complete, and give some initial results using a branch-and-bound algorithm to map two real-life cases. Initial results for two validation cases are presented for a graph-based protein surface neighbor mapping procedure that promises to provide additional spatial proximity information for the amino acid residues on the protein surface. 相似文献