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81.
Jacquelyn M. Evans Melissa L. Cox Jonathan Huska Frank Li Luis Gaitero Ling T. Guo Margaret L. Casal Henk L. Granzier G. Diane Shelton Leigh Anne Clark 《Mammalian genome》2016,27(9-10):495-502
Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches. 相似文献
82.
83.
Collectins are effector molecules of the innate immune system that play an important role in the first line of defence against bacteria, viruses and fungi. Most of their interactions with microorganisms are mediated through their carbohydrate recognition domain (CRD), which binds in a Ca(2+)-dependent manner to glycoconjugates. This domain is a well-known structure that is present in a larger group of proteins comprising the C-type lectin domain family. Collectins form a subgroup within this family based on the presence of a collagen domain and the trimerization of CRDs, which are essential for the ligand-binding properties of these proteins. The ligand specificity among the nine collectin members is significantly different as a result of both the structural organization of the trimers and specific sequence changes in the binding pocket of the CRD. In addition, some collectin members have additional features, such as N-linked glycosylation of CRD residues and additional loop structures within the CRD that have a large impact on their interaction with the glycoconjugates present on microorganisms or host cells. The availability of crystal structures of three members of the collectin family (surfactant proteins A and D and mannan-binding protein) provides an important tool for addressing the impact of these CRD differences on ligand binding. In this review, the structural differences and similarities between the CRDs of collectins are summarized and their relationship with their ligand-binding characteristics is discussed. 相似文献
84.
Britas Klemens Eriksson Tjisse van der Heide Johan van de Koppel Theunis Piersma Henk W. van der Veer Han Olff 《Ecosystems》2010,13(5):752-764
Shallow soft-sediment systems are mostly dominated by species that, by strongly affecting sediment dynamics, modify their
local environment. Such ecosystem engineering species can have either sediment-stabilizing or sediment-destabilizing effects
on tidal flats. They interplay with abiotic forcing conditions (wind, tide, nutrient inputs) in driving the community structure
and generating spatial heterogeneity, determining the composition of different communities of associated species, and thereby
affecting the channelling of energy through different compartments in the food web. This suggests that, depending on local
species composition, tidal flats may have conspicuously different geomorphology and biological functions under similar external
conditions. Here we use a historical reconstruction of benthic production in the Wadden Sea to construct a framework for the
relationships between human impacts, ecosystem engineering and sediment dynamics. We propose that increased sediment disturbances
by human exploitation interfere with biological controls of sediment dynamics, and thereby have shifted the dominant compartments
of both primary and secondary production in the Wadden Sea, transforming the intertidal from an internally regulated and spatially
heterogeneous, to an externally regulated and spatially homogenous system. This framework contributes to the general understanding
of the interaction between biological and environmental control of ecosystem functioning, and suggests a general framework
for predicting effects of human impacts on soft-bottom ecosystems. 相似文献
85.
Genetic diversity and population structure in Malus sieversii, a wild progenitor species of domesticated apple 总被引:1,自引:0,他引:1
Christopher M. Richards Gayle M. Volk Ann A. Reilley Adam D. Henk Dale R. Lockwood Patrick A. Reeves Philip L. Forsline 《Tree Genetics & Genomes》2009,5(2):339-347
Malus sieversii (Lebed.) M. Roem. is a wild progenitor species of the domesticated apple. It is found across a mountainous region of central
Asia and has been the focus of several collection expeditions by the USDA-ARS-National Plant Germplasm System. This study
used microsatellite variation at seven loci to estimate diversity and differentiation within M. sieversii using several complimentary approaches. Multilocus genotypes were amplified from 949 individuals representing seedling trees
from 88 half-sib families from eight M. sieversii populations collected in Kazakhstan. Apportioning of genetic variation was estimated at both the family and site level. Analyses
using a hierarchical model to estimate F
st showed that differentiation among individual families is more than three times greater than differentiation among sites.
In addition, average gene diversity and allelic richness varied significantly among sites. A rendering of a genetic network
among all sites showed that differentiation is largely congruent with geographical location. In addition, nonhierarchical
Bayesian assignment methods were used to infer genetic clusters across the collection area. We detected four genetic clusters
in the data set. The quality of these assignments was evaluated over multiple Markov Chain Monte Carlo runs using both posterior
likelihood and stability of the assignments. The spatial pattern of genetic assignments among the eight collection sites shows
two broadly distributed and two narrowly distributed clusters. These data indicate that the southwestern collection sites
are more admixed and more diverse than the northern sites. 相似文献
86.
Reijenga KA van Megen YM Kooi BW Bakker BM Snoep JL van Verseveld HW Westerhoff HV 《Journal of theoretical biology》2005,232(3):385-398
Biochemical oscillations, such as glycolytic oscillations, are often believed to be caused by a single so-called ‘oscillophore’. The main characteristics of yeast glycolytic oscillations, such as frequency and amplitude, are however controlled by several enzymes. In this paper, we develop a method to quantify to which extent any enzyme determines the occurrence of oscillations. Principles extrapolated from metabolic control analysis are applied to calculate the control exerted by individual enzymes on the real and imaginary parts of the eigenvalues of the Jacobian matrix. We propose that the control exerted by an enzyme on the real part of the smallest eigenvalue, in terms of absolute value, quantifies to which extent that enzyme contributes to the emergence of instability. Likewise the control exerted by an enzyme on the imaginary part of complex eigenvalues may serve to quantify the extent to which that enzyme contributes to the tendency of the system to oscillate. The method was applied both to a core model and to a realistic model of yeast glycolytic oscillations. Both the control over stability and the control over oscillatory tendency were distributed among several enzymes, of which glucose transport, pyruvate decarboxylase and ATP utilization were the most important. The distributions of control were different for stability and oscillatory tendency, showing that control of instability does not imply control of oscillatory tendency nor vice versa. The control coefficients summed up to 1, suggesting the existence of a new summation theorem. These results constitute proof that glycolytic oscillations in yeast are not caused by a single oscillophore and provide a new, subtle, definition for the oscillophore strength of an enzyme. 相似文献
87.
The aim of the study was to determine the time-dependent formation of arsenic-phytochelatin (As-PC) complexes in the roots, stems and leaves of an arsenic-nontolerant plant (Helianthus annuus) during exposure to 66 mol l(-1) arsenite (As(III)) or arsenate (As(V)). We used our previously developed method of simultaneous element-specific (inductively coupled plasma mass spectrometry, ICP-MS) and molecular-specific (electrospray-ionization mass spectrometry, ES-MS) detection systems interfaced with a suitable chromatographic column and eluent conditions, which enabled us to identify and quantify As-PC complexes directly. Roots of As-exposed H. annuus contained up to 14 different arsenic species, including the complex of arsenite with two (gamma-Glu-Cys)(2)-Gly molecules [As((III))-(PC(2))(2)], the newly identified monomethylarsonic phytochelatin-2 or (gamma-Glu-Cys)(2)-Gly CH(3)As (MA((III))-PC(2)) and at least eight not yet identified species. The complex of arsenite with (gamma-Glu-Cys)(3)-Gly (As((III))-PC(3)) and the complex of arsenite with glutathione (GSH) and (gamma-Glu-Cys)(2)-Gly (GS-As((III))-PC(2)) were present in all samples (roots, stems and leaves) taken from plants exposed to As. The GS-As((III))-PC(2) complex was the dominant complex after 1 h of exposure. As((III))-PC(3) became the predominant As-PC complex after 3 h, binding up to 40% of the As present in the exposed plants. No As-PC complexes were found in sap (mainly xylem sap from the root system), in contrast to roots, stems and leaves, which is unequivocal evidence that As-PC complexes are not involved in the translocation of As from root to leaves of H. annuus. 相似文献
88.
Fujita H Labeit D Gerull B Labeit S Granzier HL 《American journal of physiology. Heart and circulatory physiology》2004,287(6):H2528-H2534
We studied the effects of Ca2+ on titin (connectin)-based passive tension in skinned myocardium expressing either predominantly N2B titin (rat right ventricle, RRV) or predominantly N2BA titin (bovine left atrium, BLA). Actomyosin-based tension was abolished to undetectably low levels by selectively removing the thin filaments with a Ca2+-insensitive gelsolin fragment (FX-45). Myocardium was stretched in the presence and absence of Ca2+, and passive tension was measured. Ca2+ significantly increased passive tension during and after stretch in the BLA. The increase was insensitive to the actomyosin inhibitor 2,3-butanedione 2-monoxime, supporting the conclusion that the effect is titin based. Passive tension did not respond to calcium in the RRV, indicating that passive tension developed by N2B titin is calcium insensitive. Western blot analysis and immunofluorescence studies indicated that N2BA titin expresses E-rich PEVK motifs, whereas they are absent from N2B titin, supporting earlier single molecule studies that reported that E-rich motifs are required for calcium sensitivity. We conclude that calcium affects passive myocardial tension in a titin isoform-dependent manner. 相似文献
89.
90.
The RPS5 and RFL1 disease resistance genes of Arabidopsis ecotype Col-0 are oriented in tandem and are separated by 1.4 kb. The Ler-0 ecotype contains RFL1, but lacks RPS5. Sequence analysis of the RPS5 deletion region in Ler-0 revealed the presence of an Ac-like transposable element, which we have designated Tag2. Southern hybridization analysis of six Arabidopsis ecotypes revealed 4-11 Tag2-homologous sequences in each, indicating that this element is ubiquitous in Arabidopsis and has been active in recent evolutionary time. The Tag2 insertion adjacent to RFL1 was unique to the Ler-0 ecotype, however, and was not present in two other ecotypes that lack RPS5. DNA sequence from the latter ecotypes lacked a transposon footprint, suggesting that insertion of Tag2 occurred after the initial deletion of RPS5. The deletion breakpoint contained a 192-bp insertion that displayed hallmarks of a nonhomologous DNA end-joining event. We conclude that loss of RPS5 was caused by a double-strand break and subsequent repair, and cannot be attributed to unequal crossing over between resistance gene homologs. 相似文献