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91.
Moshe Goldsmith Shiri Barad Maor Knafo Alon Savidor Shifra Ben-Dor Alexander Brandis Tevie Mehlman Yoav Peleg Shira Albeck Orly Dym Efrat Ben-Zeev Ranjit S. Barbole Asaph Aharoni Ziv Reich 《The Journal of biological chemistry》2022,298(5)
Grass pea (Lathyrus sativus L.) is a grain legume commonly grown in Asia and Africa for food and forage. It is a highly nutritious and robust crop, capable of surviving both droughts and floods. However, it produces a neurotoxic compound, β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), which can cause a severe neurological disorder when consumed as a primary diet component. While the catalytic activity associated with β-ODAP formation was demonstrated more than 50 years ago, the enzyme responsible for this activity has not been identified. Here, we report on the identity, activity, 3D structure, and phylogenesis of this enzyme—β-ODAP synthase (BOS). We show that BOS belongs to the benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase superfamily of acyltransferases and is structurally similar to hydroxycinnamoyl transferase. Using molecular docking, we propose a mechanism for its catalytic activity, and using heterologous expression in tobacco leaves (Nicotiana benthamiana), we demonstrate that expression of BOS in the presence of its substrates is sufficient for β-ODAP production in vivo. The identification of BOS may pave the way toward engineering β-ODAP–free grass pea cultivars, which are safe for human and animal consumption. 相似文献
92.
Albeck S Dym O Unger T Snapir Z Bercovich Z Kahana C 《Protein science : a publication of the Protein Society》2008,17(5):793-802
Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine-induced protein, Antizyme (Az), with greater affinity than ornithine decarboxylase (ODC). AzI is highly homologous to ODC but is not enzymatically active. In order to understand these specific characteristics of AzI and its differences from ODC, we determined the 3D structure of mouse AzI to 2.05 A resolution. Both AzI and ODC crystallize as a dimer. However, fewer interactions at the dimer interface, a smaller buried surface area, and lack of symmetry of the interactions between residues from the two monomers in the AzI structure suggest that this dimeric structure is nonphysiological. In addition, the absence of residues and interactions required for pyridoxal 5'-phosphate (PLP) binding suggests that AzI does not bind PLP. Biochemical studies confirmed the lack of PLP binding and revealed that AzI exists as a monomer in solution while ODC is dimeric. Our findings that AzI exists as a monomer and is unable to bind PLP provide two independent explanations for its lack of enzymatic activity and suggest the basis for its enhanced affinity toward Az. 相似文献
93.
Marlies van Nimwegen Arlène D Speelman Katrijn Smulders Sebastiaan Overeem George F Borm Frank JG Backx Bastiaan R Bloem Marten Munneke ParkFit study group 《BMC neurology》2010,10(1):70
Background
Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity. 相似文献94.
95.
Chromosomal DNA from 23 closely related, pathogenic strains of Escherichia
coli was digested and probed for the insertion sequences IS1, IS2, IS4,
IS5, and IS30. Under the assumption that elements residing in DNA
restriction fragments of the same apparent length are identical by descent,
parsimony analysis of these characters yielded a unique phylogenetic tree.
This analysis not only distinguished among bacterial strains that were
otherwise identical in their biochemical characteristics and enzyme
electrophoretic mobilities, but certain aspects of the topology of the tree
were consistent across several unrelated insertion elements. The
distribution of IS elements was then reexamined in light of the inferred
phylogenetic relationships to investigate the biological properties of the
elements, such as rates of insertion and deletion, and to discover apparent
recombinational events. The analysis shows that the pattern of distribution
of insertion elements in the bacterial genome is sufficiently stable for
epidemiological studies. Although the rate of recombination by conjugation
has been postulated to be low, at least two such events appear to have
taken place.
相似文献
96.
97.
Janes KA Albeck JG Peng LX Sorger PK Lauffenburger DA Yaffe MB 《Molecular & cellular proteomics : MCP》2003,2(7):463-473
To treat complex human diseases effectively, a systems-level approach is needed to understand the interplay of environmental cues, intracellular signals, and cellular behaviors that underlie disease states. This approach requires high-throughput, multiplex techniques that measure quantitative temporal variations of multiple protein activities in the intracellular signaling network. Here, we describe a single microtiter-based format that simultaneously quantifies protein kinase activities in the phosphatidylinositol 3-kinase pathway (Akt), nuclear factor-kappaB pathway (IKK), and three core mitogen-activated protein kinase pathways (ERK, JNK1, MK2). These parallel high-throughput assays are stringently linear, redundantly specific, reproducible, and sensitive compared with classical low-throughput techniques. When applied to a model of sepsis-induced colon epithelial apoptosis, this approach identified a late phase of Akt activity as a critical mediator of cell survival that quantitatively contributed to the efficacy of insulin as an anti-apoptotic cue. Thus, sampling parallel nodes in the intracellular signaling network identified part of the molecular mechanism underlying the efficacy of insulin in the treatment of human sepsis. 相似文献
98.
The pKa of the catalytic His57 N(epsilon)H in the tetrahedral complex (TC) of chymotrypsin with trifluoromethyl ketone inhibitors is 4-5 units higher relative to the free enzyme (FE). Such stable TC's, formed with transition state (TS) analog inhibitors, are topologically similar to the catalytic TS. Thus, analysis of this pKa shift may shed light on the role of water solvation in the general base catalysis by histidine. We applied our QM/SCRF(VS) approach to study this shift. The method enables explicit quantum mechanical DFT calculations of large molecular clusters that simulate chemical reactions at the active site (AS) of water solvated enzymes. We derived an analytical expression for the pKa dependence on the degree of water exposure of the ionizable group, and on the total charge in the enzyme AS, Q(A) and Q(B), when the target ionizable functional group (His57 in this study) is in the acidic (A) and basic (B) forms, respectively. Q2(B) > Q2(A) both in the FE and in the TC of chymotrypsin. Therefore, water solvation decreases the relative stability of the protonated histidine in both. Ligand binding reduces the degree of water solvation of the imidazole ring, and consequently elevates the histidine pKa. Thus, the binding of the ligand plays a triggering role that switches on the cascade of catalytic reactions in serine proteases. 相似文献
99.
Background
Fairy shrimps (Anostraca), tadpole shrimps (Notostraca), clam shrimps (Spinicaudata), algae (primarily filamentous blue-green algae [cyanobacteria]), and suspended organic particulates are dominant food web components of the seasonally inundated pans and playas of the western Mojave Desert in California. We examined the extent to which these branchiopods controlled algal abundance and species composition in clay pans between Rosamond and Rogers Dry Lakes. We surveyed branchiopods during the wet season to estimate abundances and then conducted a laboratory microcosm experiment, in which dried sediment containing cysts and the overlying algal crust were inundated and cultured. Microcosm trials were run with and without shrimps; each type of trial was run for two lengths of time: 30 and 60 days. We estimated the effect of shrimps on algae by measuring chlorophyll content and the relative abundance of algal species.Results
We found two species of fairy shrimps (Branchinecta mackini and B. gigas), one tadpole shrimp (Lepidurus lemmoni), and a clam shrimp (Cyzicus setosa) in our wet-season field survey. We collected Branchinecta lindahli in a pilot study, but not subsequently. The dominant taxa were C. setosa and B. mackini, but abundances and species composition varied greatly among playas. The same species found in field surveys also occurred in the microcosm experiment. There were no significant differences as a function of experimental treatments for either chlorophyll content or algal species composition (Microcoleus vaginatus dominated all treatments).Conclusions
The results suggest that there was no direct effect of shrimps on algae. Although the pans harbored an apparently high abundance of branchiopods, these animals had little role in regulating primary producers in this environment. 相似文献100.
Y Kalechman M Albeck M Oron D Sobelman M Gurwith S N Seghal B Sredni 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(5):1512-1517
Ammonium trichloro(dioxyethylene-O-O')tellurate (AS101) is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Clinical trials are currently in progress with AS101 on AIDS and cancer patients. We found that AS101 was capable of inducing spleen cells and peritoneal exudate cells to secrete high quantities of CSF and IL-1. Because IL-1 has been previously described as a radioprotector and CSF may induce in vivo the proliferation of hemopoietic cells, we designed the present study in order to evaluate the effects of prolonged in vivo injections of AS101 on protection against lethal doses of irradiation, on the recovery pattern of precursor cells, and on the functioning of bone marrow (BM) and spleen cells of mice undergoing sublethal doses of treatment. We demonstrate that pretreatment with AS101 protects mice from lethal effects of ionizing radiation. AS101 was also found to significantly increase the number of BM and spleen cells, the absolute number of granulocyte macrophage-CFU and the secretion of CSF by BM cells. All were tested 9 days after sublethal dose of irradiation was administered. AS101 was found to have all of these radioprotective effects only when administered to mice before irradiation treatment. Moreover, the compound was found to enhance the proportion of CFU-S that enters the S phase of the cell cycle. These findings indicate that AS101 may be a promising agent to be used in reducing the time needed for reconstitution of hemopoietic cells after irradiation treatment. 相似文献