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21.
Thomae AW Baltin J Pich D Deutsch MJ Ravasz M Zeller K Gossen M Hammerschmidt W Schepers A 《Cellular and molecular life sciences : CMLS》2011,68(22):3741-3756
In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the
sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation
step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex
formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging
experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate
that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding
of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins
is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The
systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a
and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions
at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to
facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation. 相似文献
22.
Host defense peptides and proteins are important components of the innate host defense against pathogenic microorganisms.
They target negatively charged bacterial surfaces and disrupt microbial cytoplasmic membranes, which ultimately leads to bacterial
destruction. Throughout evolution, pathogens devised several mechanisms to protect themselves from deleterious damage of host
defense peptides. These strategies include (a) inactivation and cleavage of host defense peptides by production of host defense
binding proteins and proteases, (b) repulsion of the peptides by alteration of pathogen’s surface charge employing modifications
by amino acids or amino sugars of anionic molecules (e.g., teichoic acids, lipid A and phospholipids), (c) alteration of bacterial
membrane fluidity, and (d) expulsion of the peptides using multi drug pumps. Together with bacterial regulatory network(s)
that regulate expression and activity of these mechanisms, they represent attractive targets for development of novel antibacterials. 相似文献
23.
Fluctuations in the counting rate of photons originating from uncorrelated point sources become, within the coherently illuminated area, slightly enhanced compared to a random sequence of classical particles. This phenomenon, known in astronomy as the Hanbury Brown-Twiss effect, is a consequence of quantum interference between two indistinguishable photons and Bose Einstein statistics. The latter require that the composite bosonic wavefunction is a symmetric superposition of the two possible paths. For fermions, the corresponding two-particle wavefunction is antisymmetric: this excludes overlapping wave trains, which are forbidden by the Pauli exclusion principle. Here we use an electron field emitter to coherently illuminate two detectors, and find anticorrelations in the arrival times of the free electrons. The particle beam has low degeneracy (about 10(-4) electrons per cell in phase space); as such, our experiment represents the fermionic twin of the Hanbury Brown-Twiss effect for photons. 相似文献
24.
25.
Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献
26.
Kalscheuer VM Freude K Musante L Jensen LR Yntema HG Gécz J Sefiani A Hoffmann K Moser B Haas S Gurok U Haesler S Aranda B Nshedjan A Tzschach A Hartmann N Roloff TC Shoichet S Hagens O Tao J Van Bokhoven H Turner G Chelly J Moraine C Fryns JP Nuber U Hoeltzenbein M Scharff C Scherthan H Lenzner S Hamel BC Schweiger S Ropers HH 《Nature genetics》2003,35(4):313-315
We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder. 相似文献
27.
Convergent evolution of gene circuits 总被引:9,自引:0,他引:9
28.
Kohl I Bachmann L Mayer E Hallbrucker A Loerting T 《Nature》2005,435(7041):E1; discussion E1-E1; discussion E2
It has been unclear whether amorphous glassy water heated to around 140-150 K remains glassy until it crystallizes or whether instead it turns into a supercooled and very viscous liquid. Yue and Angell compare the behaviour of glassy water under these conditions to that of hyperquenched inorganic glasses, and claim that water stays glassy as it heats up to its crystallization point; they also find a 'hidden' glass-to-liquid transition at about 169 K. Here we use differential scanning calorimetry (DSC) heating to show that hyperquenched water deposited at 140 K behaves as an ultraviscous liquid, the limiting structure of which depends on the cooling rate--as predicted by theoretical analysis of the liquid-to-glass transition. Our findings are consistent with a glass-to-liquid transition-onset temperature (T(g)) in the region of 136 K (refs 3,4), and they indicate that measurements of the liquid's properties may clarify the anomalous properties of supercooled water. 相似文献
29.
Cryptic variation is caused by the robustness of phenotypes to mutations. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change. Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation. This is possible if the cryptic variation happens to be pre-adapted, or "exapted", to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution. 相似文献
30.
Rasmussen SG Choi HJ Fung JJ Pardon E Casarosa P Chae PS Devree BT Rosenbaum DM Thian FS Kobilka TS Schnapp A Konetzki I Sunahara RK Gellman SH Pautsch A Steyaert J Weis WI Kobilka BK 《Nature》2011,469(7329):175-180
G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation. 相似文献