全文获取类型
收费全文 | 1119篇 |
免费 | 85篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 21篇 |
2020年 | 15篇 |
2019年 | 13篇 |
2018年 | 29篇 |
2017年 | 3篇 |
2016年 | 14篇 |
2015年 | 38篇 |
2014年 | 53篇 |
2013年 | 84篇 |
2012年 | 95篇 |
2011年 | 75篇 |
2010年 | 53篇 |
2009年 | 62篇 |
2008年 | 94篇 |
2007年 | 100篇 |
2006年 | 77篇 |
2005年 | 76篇 |
2004年 | 65篇 |
2003年 | 71篇 |
2002年 | 59篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 15篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1204条查询结果,搜索用时 31 毫秒
101.
102.
Salavat?R. Nabiev Denis?A. Ovsyannikov Galina?V. Kopylova Daniil?V. Shchepkin Alexander?M. Matyushenko Natalia?A. Koubassova Dmitrii?I. Levitsky Andrey?K. Tsaturyan Sergey?Y. Bershitsky 《Biophysical journal》2015,109(2):373-379
A two-beam optical trap was used to measure the bending stiffness of F-actin and reconstructed thin filaments. A dumbbell was formed by a filament segment attached to two beads that were held in the two optical traps. One trap was static and held a bead used as a force transducer, whereas an acoustooptical deflector moved the beam holding the second bead, causing stretch of the dumbbell. The distance between the beads was measured using image analysis of micrographs. An exact solution to the problem of bending of an elastic filament attached to two beads and subjected to a stretch was used for data analysis. Substitution of noncanonical residues in the central part of tropomyosin with canonical ones, G126R and D137L, and especially their combination, caused an increase in the bending stiffness of the thin filaments. The data confirm that the effect of these mutations on the regulation of actin-myosin interactions may be caused by an increase in tropomyosin stiffness. 相似文献
103.
Alexey?A. Malygin Dmitri?M. Graifer Maria?I. Meschaninova Aliya?G. Venyaminova Olesya?A. Krumkacheva Matvey?V. Fedin Galina?G. Karpova Elena?G. Bagryanskaya 《Biophysical journal》2015,109(12):2637-2643
mRNAs are involved in complicated supramolecular complexes with human 40S and 80S ribosomes responsible for the protein synthesis. In this work, a derivative of nonaribonucleotide pUUCGUAAAA with nitroxide spin labels attached to the 5′-phosphate and to the C8 atom of the adenosine in sixth position (mRNA analog) was used for studying such complexes using double electron-electron resonance/pulsed electron-electron double resonance spectroscopy. The complexes were assembled with participation of tRNAPhe, which targeted triplet UUC of the derivative to the ribosomal peptidyl site and predetermined location of the adjacent GUA triplet coding for Val at the aminoacyl (A) site. The interspin distances were measured between the two labels of mRNA analog attached to the first nucleotide of the peptidyl site bound codon and to the third nucleotide of the A site bound codon, in the absence/presence of second tRNA bound at the A site. The values of the obtained interspin distances agree with those calculated for available near-atomic structures of similar complexes of 40S and 80S ribosomes, showing that neither 60S subunit nor tRNA at the A site have a noticeable effect on arrangement of mRNA at the codon-anticodon interaction area. In addition, the shapes of distance distributions in four studied ribosomal complexes allowed conclusions on conformational flexibility of mRNA in these complexes. Overall, the results of this study are the first, to our knowledge, demonstration of double electron-electron resonance/pulsed electron-electron double resonance application for measurements of intramolecular distances in multicomponent supramolecular complexes involving intricate cellular machineries and for evaluating dynamic properties of ligands bound to these machineries. 相似文献
104.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
105.
Xi Chen Kathrin Hnida Melissa Ann Graewert Jan Terje Andersen Rasmus Iversen Anne Tuukkanen Dmitri Svergun Ludvig M. Sollid 《The Journal of biological chemistry》2015,290(35):21365-21375
Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. 相似文献
106.
Elena M. Pugacheva Samuel Rivero-Hinojosa Celso A. Espinoza Claudia Fabiola Méndez-Catalá Sungyun Kang Teruhiko Suzuki Natsuki Kosaka-Suzuki Susan Robinson Vijayaraj Nagarajan Zhen Ye Abdelhalim Boukaba John E. J. Rasko Alexander V. Strunnikov Dmitri Loukinov Bing Ren Victor V. Lobanenkov 《Genome biology》2015,16(1)
107.
The emergence of astroglia as an important participant of the synaptic machinery has led to the 'tripartite synapse' hypothesis. Recent findings suggest that synaptic signaling also involves the surrounding extracellular matrix (ECM). The ECM can incorporate and store molecular traces of both neuronal and glial activities. It can also modulate function of local receptors or ion channels and send diffuse molecular signals using products of its use-dependent proteolytic cleavage. Recent experimental findings implicate the ECM in mechanisms of synaptic plasticity and glial remodeling, thus lending support to the 'tetrapartite synapse' concept. This inclusive view might help to understand better the mechanisms underlying signal integration and novel forms of long-term homeostatic regulation in the brain. 相似文献
108.
Dmitriev RI Ropiak HM Ponomarev GV Yashunsky DV Papkovsky DB 《Bioconjugate chemistry》2011,22(12):2507-2518
A panel of phosphorescent oligoarginine conjugates of tetracarboxylic Pt(II)-coproporphyrin I dye (PtCP), monosubstituted with long peptides or tetra-substituted with short peptides and having different linkers and peripheral groups, is described. Their photophysical properties, cell loading efficiency, and mechanisms of transport into the cell were investigated and compared. The conjugates were seen to rely on endocytotic mechanisms of cell entry, which are different from that of the unconjugated oligoarginine peptide, and show diverse patterns of intracellular distribution. On the basis of this study, the tetra-substituted PtCP conjugate displaying whole cell distribution was selected for the sensing of intracellular O(2). This probe has been tested in biological experiments on a fluorescence plate reader, including the monitoring of in situ oxygenation of respiring cells and their responses to metabolic stimulation. Similar conjugates of the phosphorescent Pd(II)-coprorphyrin and fluorescent coproporphyrin-ketone were also synthesized and assessed for the sensing of low levels intracellular O(2) and ratiometric pH-sensing, respectively. The results produced and the structure-activity relationships determined can facilitate the rational design of new bioconjugates of porphyrin dyes tailored to specific applications. 相似文献
109.
110.
Healthy young adults transition between level and hill surfaces of various angles while walking at fluctuating speeds. These surface transitions have the potential to decrease dynamic balance in both the anterior-posterior and medial-lateral directions. Hence, the purpose of the current study was to analyze modifications in temporal-spatial parameters during hill walking transitions. We hypothesized that in comparison with level walking, the transition strides would indicate the adoption of a distinct gait strategy with a greater base of support. Thirty-four participants completed level and hill trials on a walkway with a 15-degree portable ramp apparatus. We collected data during 4 transition strides between level and ramp surfaces. In support of our hypothesis, compared with level walking, the base of support was 20% greater during 3 out of the 4 transition strides. In short, our results illustrate that healthy young adults did adopt a distinct gait strategy different from both level and hill walking during transitions strides. 相似文献