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51.
52.
A set of proteins and noncoding RNAs,referred to as the male specific lethal (MSL) complex,is present on the male X chromosome in Drosophila and has been postulated to be responsible for dosage compensation of this chromosome - the up-regulation of its expression to be equal to that of two X chromosomes in females.This hypothesis is evaluated in view of lesser known aspects of dosage compensation such as the fact that metafemales with three X chromosomes also have equal expression to normal females,which would require a down-regulation of each gene copy.Moreover,when this complex is ectopically expressed in females or specifically targeted to a reporter in males,there is no increase in expression of the genes or targets with which it is associated.These observations are not consistent with the hypothesis that the MSL complex conditions dosage compensation.A synthesis is described that can account for these observations. 相似文献
53.
Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome
is different in males and females. In Drosophila there is a twofold upregulation of the single male X. In triple X metafemales, there is also dosage compensation, which occurs
by a two-thirds downregulation. There is a concomitant reduction in expression of many autosomal genes in metafemales. The
male specific lethal (MSL) complex is present on the male X chromosome. Evidence is discussed showing that the MSL complex
sequesters a histone acetyltransferase to the X chromosome to mute an otherwise increased expression by diminishing the histone
acetylation on the autosomes. Several lines of evidence indicate that a constraining activity occurs from the MSL complex
to prevent overcompensation on the X that might otherwise occur from the high level of acetylation present. Together, the
evidence suggests that dosage compensation is a modification of a regulatory inverse dosage effect that is a reflection of
intrinsic gene regulatory mechanisms and that the MSL complex has evolved in reaction in order to equalize the expression
on both the X and autosomes of males and females. 相似文献
54.
55.
The trace version of classical conditioning is used as a prototypical hippocampal-dependent task to study the recoding sequence prediction theory of hippocampal function. This theory conjectures that the hippocampus is a random recoder of sequences and that, once formed, the neuronal codes are suitable for prediction. As such, a trace conditioning paradigm, which requires a timely prediction, seems by far the simplest of the behaviorally-relevant paradigms for studying hippocampal recoding. Parameters that affect the formation of these random codes include the temporal aspects of the behavioral/cognitive paradigm and certain basic characteristics of hippocampal region CA3 anatomy and physiology such as connectivity and activity. Here we describe some of the dynamics of code formation and describe how biological and paradigmatic parameters affect the neural codes that are formed. In addition to a backward cascade of coding neurons, we point out, for the first time, a higher-order dynamic growing out of the backward cascade—a particular forward and backward stabilization of codes as training progresses. We also observe that there is a performance compromise involved in the setting of activity levels due to the existence of three behavioral failure modes. Each of these behavioral failure modes exists in the computational model and, presumably, natural selection produced the compromise performance observed by psychologists. Thus, examining the parametric sensitivities of the codes and their dynamic formation gives insight into the constraints on natural computation and into the computational compromises ensuing from these constraints. 相似文献
56.
Burgess KL Corbett MS Eugenio P Lajkiewicz NJ Liu X Sanyal A Yan W Yuan Q Snyder JK 《Bioorganic & medicinal chemistry》2005,13(17):5299-5309
The development of chiral anthracene templates for use in Diels-Alder/retro Diels-Alder sequences is described. A summary of past results and new progress is reported. 相似文献
57.
Analysis of conditional paralytic mutants in Drosophila sarco-endoplasmic reticulum calcium ATPase reveals novel mechanisms for regulating membrane excitability
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Sanyal S Consoulas C Kuromi H Basole A Mukai L Kidokoro Y Krishnan KS Ramaswami M 《Genetics》2005,169(2):737-750
Individual contributions made by different calcium release and sequestration mechanisms to various aspects of excitable cell physiology are incompletely understood. SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. By isolation and extensive characterization of conditional mutations in the Drosophila SERCA gene, we describe novel roles of this key protein in neuromuscular physiology and enable a genetic analysis of SERCA function. At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. This suggests a direct contribution of store-derived calcium in determining the quantal content of evoked release. Conditional paralysis of SERCA mutants is also marked by prolonged neural activity-driven muscle contraction, thus reflecting the phylogenetically conserved role of SERCA in terminating contraction. Further analysis of ionic currents from mutants uncovers SERCA-dependent mechanisms regulating voltage-gated calcium channels and calcium-activated potassium channels that together control muscle excitability. Finally, our identification of dominant loss-of-function mutations in SERCA indicates novel intra- and intermolecular interactions for SERCA in vivo, overlooked by current structural models. 相似文献
58.
Jain DS Subbaiah G Sanyal M Pande UC Shrivastav P 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,837(1-2):92-100
A high throughput bioanalytical method based on solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS), has been developed for the estimation of perindopril and its metabolite perindoprilat, an angiotensin-converting enzyme inhibitor in human plasma. Ramipril was used as internal standard (IS). The extraction of perindopril, perindoprilat and ramipril from the plasma involved treatment with phosphoric acid followed by solid phase extraction (SPE) using hydrophilic lipophilic balance HLB cartridge. The SPE eluate without drying were analyzed by LC-MS/MS, equipped with turbo ion spray (TIS) source, operating in the negative ion and selective reaction monitoring (SRM) acquisition mode to quantify perindopril and perindoprilat in human plasma. The total chromatographic run time was 1.5 min with retention time for perindopril, perindoprilat and ramipril at 0.33, 0.35 and 0.30 min. The developed method was validated in human plasma matrix, with a sensitivity of 0.5 ng/ml (CV, 7.67%) for perindopril and 0.3 ng/ml (CV, 4.94%) for perindoprilat. This method was extensively validated for its accuracy, precision, recovery, stability studies and matrix effect especially because the pattern of elution of all the analytes appears as flow injection elution. Sample preparation by this method yielded extremely clean extracts with very good and consistent mean recoveries; 78.29% for perindopril, 76.32% for perindoprilat and 77.72% for IS. The response of the LC-MS/MS method for perindopril and perindoprilat was linear over the range 0.5-350.0 ng/ml for perindopril and 0.3-40 ng/ml for perindoprilat with correlation coefficient, r>/=0.9998 and 0.9996, respectively. The method was successfully applied for bioequivalence studies in human subjects samples with 4 mg immediate release (IR) formulations. 相似文献
59.
Mechanisms of genome evolution are poorly understood although recent genome sequencing is providing the tools to begin to
illuminate such mechanisms. Using high-resolution molecular cytogenetic tools, we examined the structural evolution of 790 kb
surrounding the evolutionarily important FLC locus of Arabidopsis thaliana in three of its relatives, Arabidopsis halleri, Arabidopsis neglecta and Arabidopsis arenosa. Sequenced BACs from A. thaliana were used as heterologous probes across these species and genome expansion was found in all three species relative to A. thaliana, ranging from 16 to 27%. Expansion was seen along the length of the entire region but molecular analyses revealed no characteristic
pattern of either intra- or intergenic expansion among these species. Mapping of BACs on DNA fibers from A. thaliana revealed one possible error, ~14 kb missing from the reported sequence, indicating that for comparative studies it is important
to confirm the reference sequence to which comparison will be made. 相似文献
60.
The functional significance of ribosomal proteins is still relatively unclear. Here, we examined the role of small subunit protein S20 in translation using both in vivo and in vitro techniques. By means of lambda red recombineering, the rpsT gene, encoding S20, was removed from the chromosome of Salmonella enterica var. Typhimurium LT2 to produce a ΔS20 strain that grew markedly slower than the wild type while maintaining a wild-type rate of peptide elongation. Removal of S20 conferred a significant reduction in growth rate that was eliminated upon expression of the rpsT gene on a high-copy-number plasmid. The in vitro phenotype of mutant ribosomes was investigated using a translation system composed of highly active, purified components from Escherichia coli. Deletion of S20 conferred two types of initiation defects to the 30S subunit: (i) a significant reduction in the rate of mRNA binding and (ii) a drastic decrease in the yield of 70S complexes caused by an impairment in association with the 50S subunit. Both of these impairments were partially relieved by an extended incubation time with mRNA, fMet-tRNAfMet, and initiation factors, indicating that absence of S20 disturbs the structural integrity of 30S subunits. Considering the topographical location of S20 in complete 30S subunits, the molecular mechanism by which it affects mRNA binding and subunit docking is not entirely obvious. We speculate that its interaction with helix 44 of the 16S ribosomal RNA is crucial for optimal ribosome function. 相似文献