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排序方式: 共有205条查询结果,搜索用时 31 毫秒
151.
Liu Q Smith MA Avilá J DeBernardis J Kansal M Takeda A Zhu X Nunomura A Honda K Moreira PI Oliveira CR Santos MS Shimohama S Aliev G de la Torre J Ghanbari HA Siedlak SL Harris PL Sayre LM Perry G 《Free radical biology & medicine》2005,38(6):746-754
Several recent studies support a link between tau protein phosphorylation and adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent adduction of tau by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified tau are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of tau in Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These findings not only support the idea that oxidative stress is involved in neurofibrillary tangle formation occurring in brains of Alzheimer disease patients, but also show, for the first time, that HNE modifications of tau promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles. 相似文献
152.
The unabi (Zizyphus Mill) fruit extract as well as a composite preparation produced on its base in proportional mix with the extract of germinating wheat seed embryos were determined on antimutagenous activity in model experiments with laboratory animals. The specified gene-protected properties of the preparation were approved against the influence of work place environmental factors in chemical and textile industries. 相似文献
153.
The kinetics of exchange of adenine nucleotides in a system with reconstituted mitochondrial adenine nucleotide translocase (ANT) was simulated mathematically to analyze the basic mechanisms of ANT functioning. Two known alternative kinetic schemes were analyzed, the ping-pong type scheme with single-center substrate binding and the scheme of sequential two-center substrate binding at opposite sides of ANT. According to our modeling, both schemes can explain the experimental data on the adenine nucleotide exchange in the reconstituted ANT system. However, the characteristic kinetic pattern of ADP exchanges in the mono exchange mode was reproduced only by the sequential binding scheme. This scheme is consistent with the data on the tetrameric structure of ANT. On the other hand, only the single-center binding scheme was compatible with recent data on possible translocation of ATP and ADP by the carrier that has no bound adenine nucleotide on its opposite side. Based on the analysis of the literature data on ANT properties, a compromise scheme of ANT operation was proposed. In the framework of this scheme, the ANT dimers function by the single-center binding mechanism: however, in tetramers they are integrated into a substructure with two oppositely oriented binding centers working by the mechanism of sequential substrate binding. Labile bonds between the ANT-forming dimers could allow conformational rearrangements of ANT induced by various influences on mitochondrial membrane structure, including those leading to the induction of permeability transition pores in apoptosis. 相似文献
154.
A simple nonlinear model of electrical activity in the intestine 总被引:5,自引:0,他引:5
We have simulated electrical activity of the intestine in a computer model that describes the coupled layers of longitudinal muscle (LM) and interstitial cells of Cajal (ICC). The model suggests that pacemaker activity is due to the ICC layer, while the pulse propagation involves the LM layer that is in the excitatory state. The model describes well the experimentally observed phenomena: frequency change along the intestine, synchronization along short distances and desynchronization for long distances, and the decrease of propagation distance and propagation time along the intestine. We have observed the occurrence of phase interruptions or breaks, which are responsible for the limited values of propagation distance and time. 相似文献
155.
Abil E. Aliev Martin Kulke Harmeet S. Khaneja Vijay Chudasama Tom D. Sheppard Rachel M. Lanigan 《Proteins》2014,82(2):195-215
We propose a new approach for force field optimizations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use 13C NMR spin‐lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4‐hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius‐type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force‐field (termed as AMBER99SB‐ILDNP) against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimization. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. Proteins 2014; 82:195–215. © 2013 Wiley Periodicals, Inc. 相似文献
156.
Paulo Breinis Flavio Geraldes Alves Camila AE Alves Rafael G Cintra Débora Almeida Priscila C Passarelli Camila Domingues Talita Gerbim Régia Gasparetto Luiz Carlos de Abreu Vitor E Valenti Adriana Gonçalves de Oliveira Carlos Bandeira de Mello Monteiro Rubens Wajnzstejn 《BMC neurology》2014,14(1):1-4
Background
The Mulvihill-Smith Syndrome was first recognized in 1975. After the recognition of the Mulvihill-Smith Syndrome, ten cases have been described.Case presentation
This article describes the eleventh case of this syndrome in a male patient, 24 years-old with short stature and microcephaly with mild cognitive impairment, deafness and allergic conjunctivitis. The patient was hospitalized several times for repeated infections, and the presence of multiple melanocytic nevi on his skin was noticed.Conclusions
Based on the entire set of signs and symptoms presented in our study, it was diagnosed the patient with Mulvihill-Smith Syndrome. 相似文献157.
Philipp Diebolder Armin Keller Stephanie Haase Anne Schlegelmilch Jonathan D Kiefer Tamana Karimi Tobias Weber Gerhard Moldenhauer Roland Kehm Anna M Eis-Hübinger Dirk J?ger Philippe A Federspil Christel Herold-Mende Gerhard Dyckhoff Roland E Kontermann Michaela AE Arndt Jürgen Krauss 《MABS-AUSTIN》2014,6(1):130-142
The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential. 相似文献
158.
159.
160.
Roosa AE Laitinen Suvi Broholm Victor A Albert Teemu H Teeri Paula Elomaa 《BMC plant biology》2006,6(1):11-18