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211.
A method is presented to predict overall conformations of protein-DNA complexes on the basis of the known three-dimensional structures of the proteins. The method is restricted to proteins with a common twofold symmetry axis, which show only minor conformational changes upon binding to DNA. The method uses a numerical finite difference solution of the linearized Poisson-Boltzmann equation and subsequent energy minimization cycles. Structural parameters—the rotation angle of the DNA relative to the protein around the common symmetry axis, the protein-DNA distance, and intermolecular hydrogen-bonding contacts—are presented for two test cases, DNA bound to CAP (catabolite gene activator protein) and to the Cro-repressor of bacteriophage 434. The DNA curvature in the starting model of the docking procedure was chosen as a smoothed approximation of the conformation found in the X-ray structures of these complexes. The method is further used to predict the unknown structure of the complex between the factor for inversion stimulation (FIS) and DNA, which is bent upon binding to FIS. In contrast to the test cases, the unknown curvature of the starting model is derived from a calibration of electrostatic precalculations for different proteins according to crystallographically observed DNA bending. The results of the modeling are in good accordance with the experimentally observed overall structure of protein-DNA complexes for the two test cases; for FIS, they correspond to several of the experimentally proposed protein-DNA contacts. © 1996 Wiley-Liss, Inc. 相似文献
212.
Barbara Safaric Erika Chacin Matthias J Scherr Lional Rajappa Christian Gebhardt Christoph
F Kurat Thorben Cordes Karl E Duderstadt 《Nucleic acids research》2022,50(3):1317
Chromosome replication depends on efficient removal of nucleosomes by accessory factors to ensure rapid access to genomic information. Here, we show this process requires recruitment of the nucleosome reorganization activity of the histone chaperone FACT. Using single-molecule FRET, we demonstrate that reorganization of nucleosomal DNA by FACT requires coordinated engagement by the middle and C-terminal domains of Spt16 and Pob3 but does not require the N-terminus of Spt16. Using structure-guided pulldowns, we demonstrate instead that the N-terminal region is critical for recruitment by the fork protection complex subunit Tof1. Using in vitro chromatin replication assays, we confirm the importance of these interactions for robust replication. Our findings support a mechanism in which nucleosomes are removed through the coordinated engagement of multiple FACT domains positioned at the replication fork by the fork protection complex. 相似文献
213.
María Moreno-Villanueva Ragen Pfeiffer Thilo Sindlinger Alan Leake Marcus Müller Thomas BL Kirkwood Alexander Bürkle 《BMC biotechnology》2009,9(1):39-9
Background
Formation and repair of DNA single-strand breaks are important parameters in the assessment of DNA damage and repair occurring in live cells. The 'Fluorimetric Detection of Alkaline DNA Unwinding (FADU)' method [Birnboim HC, Jevcak JJ. Cancer Res (1981) 41:1889–1892] is a sensitive procedure to quantify DNA strand breaks, yet it is very tedious to perform. 相似文献214.
The ecological and evolutionary processes that interact to shape community structure are poorly studied in the largest environment on earth, the deep sea. Phylogenetic data and morphological traits of octocorals were coupled with environmental factors to test hypotheses of community assembly in the deep (250–2500 m) Gulf of Mexico. We found lineage turnover at a depth of 800–1200 m, with isidids and chrysogorgiids at deeper depths and a diversity of species from across the phylogeny occupying shallower depths. Traits, including axis type, polyp shape, and polyp retraction, differed among species occupying the shallowest (250–800 m) and deepest (1200–2500 m) depths. Results also indicated that octocoral species sort along an environmental gradient of depth. Closely related octocoral species sorted into different depth strata on the upper to middle slope, likely due to barriers imposed by water masses followed by adaptive divergence. Within any given depth zone down to 2000 m, the phylogenetic relatedness of co-existing octocorals was random, indicating that stochastic processes, such as recruitment, also shape community structure. At depths >2000 m, octocorals were more closely related than expected by chance due to the diversification of chrysogorgiids and isidids, which retain conserved traits that impart survival at deeper and/or colder depths. Polyp density, size, and inter-polyp distance were significantly correlated with depth, particularly in plexaurids and isidids, highlighting trait lability across depth and supporting that environmental gradients influence octocoral morphology. Our community phylogenetics approach indicates that both environmental filtering and neutral processes shape community assembly in the deep sea. 相似文献
215.
Thomas Güttler Metin Aksu Antje Dickmanns Kim M. Stegmann Kathrin Gregor Renate Rees Waltraud Taxer Oleh Rymarenko Jürgen Schünemann Christian Dienemann Philip Gunkel Bianka Mussil Jens Krull Ulrike Teichmann Uwe Groß Volker C Cordes Matthias Dobbelstein Dirk Grlich 《The EMBO journal》2021,40(19)
Monoclonal anti‐SARS‐CoV‐2 immunoglobulins represent a treatment option for COVID‐19. However, their production in mammalian cells is not scalable to meet the global demand. Single‐domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor‐binding domain (RBD) of the SARS‐CoV‐2 Spike protein, we isolated 45 infection‐blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS‐CoV‐2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X‐ray and cryo‐EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune‐escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low‐picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold‐promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape‐mutations. 相似文献
216.
Graeme Shannon Phoebe Sadler Joanna Smith Eleanor Roylance-Casson Line S. Cordes 《Biology letters》2021,17(10)
Sexual size dimorphism (SSD) is a common morphological trait in ungulates, with polygyny considered the leading driver of larger male body mass and weapon size. However, not all polygynous species exhibit SSD, while molecular evidence has revealed a more complex relationship between paternity and mating system than originally predicted. SSD is, therefore, likely to be shaped by a range of social, ecological and physiological factors. We present the first definitive analysis of SSD in the common hippopotamus (Hippopotamus amphibius) using a unique morphological dataset collected from 2994 aged individuals. The results confirm that hippos exhibit SSD, but the mean body mass differed by only 5% between the sexes, which is rather limited compared with many other polygynous ungulates. However, jaw and canine mass are significantly greater in males than females (44% and 81% heavier, respectively), highlighting the considerable selection pressure for acquiring larger weapons. A predominantly aquatic lifestyle coupled with the physiological limitations of their foregut fermenting morphology likely restricts body size differences between the sexes. Indeed, hippos appear to be a rare example among ungulates whereby sexual selection favours increased weapon size over body mass, underlining the important role that species-specific ecology and physiology have in shaping SSD. 相似文献
217.
218.
The nuclear basket (NB), anchored to the nuclear pore complex (NPC), is commonly looked upon as a structure built solely of protein TPR polypeptides, the latter thus regarded as the NB’s only scaffold-forming components. In the current study, we report ZC3HC1 as a second structural element of the NB. Recently described as an NB-appended protein omnipresent in vertebrates, we now show that ZC3HC1, both in vivo and in vitro, enables in a stepwise manner the recruitment of TPR subpopulations to the NB and their linkage to already NPC-anchored TPR polypeptides. We further demonstrate that the degron-mediated rapid elimination of ZC3HC1 results in the prompt detachment of the ZC3HC1-appended TPR polypeptides from the NB and their release into the nucleoplasm, underscoring the role of ZC3HC1 as a natural structural element of the NB. Finally, we show that ZC3HC1 can keep TPR polypeptides positioned and linked to each other even at sites remote from the NB, in line with ZC3HC1 functioning as a protein connecting TPR polypeptides. 相似文献
219.
Guillaume Bouvignies Dmitry M. Korzhnev Philipp Neudecker D. Flemming Hansen Matthew H. J. Cordes Lewis E. Kay 《Journal of biomolecular NMR》2010,47(2):135-141
NMR relaxation dispersion spectroscopy is a powerful method for studying protein conformational dynamics whereby visible,
ground and invisible, excited conformers interconvert on the millisecond time-scale. In addition to providing kinetics and
thermodynamics parameters of the exchange process, the CPMG dispersion experiment also allows extraction of the absolute values
of the chemical shift differences between interconverting states,
| \Updelta [(w)\tilde] | \left| {\Updelta \tilde{\omega }} \right| , opening the way for structure determination of excited state conformers. Central to the goal of structural analysis is the
availability of the chemical shifts of the excited state that can only be obtained once the signs of
\Updelta [(w)\tilde] \Updelta \tilde{\omega } are known. Herein we describe a very simple method for determining the signs of 1HN
\Updelta [(w)\tilde] \Updelta \tilde{\omega } values based on a comparison of peak positions in the directly detected dimensions of a pair of 1HN–15N correlation maps recorded at different static magnetic fields. The utility of the approach is demonstrated for three proteins
that undergo millisecond time-scale conformational rearrangements. Although the method provides fewer signs than previously
published techniques it does have a number of strengths: (1) Data sets needed for analysis are typically available from other
experiments, such as those required for measuring signs of 15N
\Updelta [(w)\tilde] \Updelta \tilde{\omega } values, thus requiring no additional experimental time, (2) acquisition times in the critical detection dimension can be
as long as necessary and (3) the signs obtained can be used to cross-validate those from other approaches. 相似文献