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131.
Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance 总被引:6,自引:0,他引:6
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Prandini P Deutsch S Lyle R Gagnebin M Delucinge Vivier C Delorenzi M Gehrig C Descombes P Sherman S Dagna Bricarelli F Baldo C Novelli A Dallapiccola B Antonarakis SE 《American journal of human genetics》2007,81(2):252-263
Down syndrome (DS) is characterized by extensive phenotypic variability, with most traits occurring in only a fraction of affected individuals. Substantial gene-expression variation is present among unaffected individuals, and this variation has a strong genetic component. Since DS is caused by genomic-dosage imbalance, we hypothesize that gene-expression variation of human chromosome 21 (HSA21) genes in individuals with DS has an impact on the phenotypic variability among affected individuals. We studied gene-expression variation in 14 lymphoblastoid and 17 fibroblast cell lines from individuals with DS and an equal number of controls. Gene expression was assayed using quantitative real-time polymerase chain reaction on 100 and 106 HSA21 genes and 23 and 26 non-HSA21 genes in lymphoblastoid and fibroblast cell lines, respectively. Surprisingly, only 39% and 62% of HSA21 genes in lymphoblastoid and fibroblast cells, respectively, showed a statistically significant difference between DS and normal samples, although the average up-regulation of HSA21 genes was close to the expected 1.5-fold in both cell types. Gene-expression variation in DS and normal samples was evaluated using the Kolmogorov-Smirnov test. According to the degree of overlap in expression levels, we classified all genes into 3 groups: (A) nonoverlapping, (B) partially overlapping, and (C) extensively overlapping expression distributions between normal and DS samples. We hypothesize that, in each cell type, group A genes are the most dosage sensitive and are most likely involved in the constant DS traits, group B genes might be involved in variable DS traits, and group C genes are not dosage sensitive and are least likely to participate in DS pathological phenotypes. This study provides the first extensive data set on HSA21 gene-expression variation in DS and underscores its role in modulating the outcome of gene-dosage imbalance. 相似文献
132.
Metformin monotherapy in melanoma: a pilot,open‐label,prospective, and multicentric study indicates no benefit
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Henri Montaudié Michael Cerezo Philippe Bahadoran Coralie Roger Thierry Passeron Laurent Machet Jean‐Philippe Arnault Laurence Verneuil Eve Maubec François Aubin Florence Granel Damien Giacchero Véronique Hofman Jean‐Philippe Lacour Allegra Maryline Stéphane Rocchi 《Pigment cell & melanoma research》2017,30(3):378-380
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134.
Spontaneous alternation in a T maze was studied as a one trial learning paradigm in mice of the BALB/c strain. In the first experiment the combined effects of time interval between the first and second trial (intertrial interval: ITI), food deprivation and feeding given during the first trial, were shown to affect performance. Thus, on the one hand, the percentage of spontaneous alternation decreased as ITI increased; on the other hand, food reward dramatically improved spontaneous alternation for the 24-h ITI, but had no significant effect for 30-sec and 1-h ITI. Since the effect of feeding might be due either to an increase of arousal, thus favoring input of informations associated with the first choice, or to an improvement in memory consolidation, a second experiment was aimed at testing the effect of food given after the first trial. It was shown that, as in the first experiment, post-trial feeding improved spontaneous alternation on the second trial given 24 hours later with a temporal gradient of effect less than 30 min. These results clearly showed that the reinforcement of run to one side (first trial) increased the tendency to go to the other side 24 hours later. It is concluded that reinforcement might have two distinct effects: (i) according to SR theory, reinforcement increases conditioned responses and (ii), as shown here, acts on memory processes by preventing memory traces from fading. The fact that this last effect was only observed for long ITI suggests that short-term or transient memory and long-term memory are two relatively independent processes. 相似文献
135.
Charlene Rivera Sara J. S. Simonson Idella F. Yamben Shalini Shatadal Minh M. Nguyen Maryline Beurg Paul F. Lambert Anne E. Griep 《PloS one》2013,8(1)
The development of specialized organs is tightly linked to the regulation of cell growth, orientation, migration and adhesion during embryogenesis. In addition, the directed movements of cells and their orientation within the plane of a tissue, termed planar cell polarity (PCP), appear to be crucial for the proper formation of the body plan. In Drosophila embryogenesis, Discs large (dlg) plays a critical role in apical-basal cell polarity, cell adhesion and cell proliferation. Craniofacial defects in mice carrying an insertional mutation in Dlgh-1 suggest that Dlgh-1 is required for vertebrate development. To determine what roles Dlgh-1 plays in vertebrate development, we generated mice carrying a null mutation in Dlgh-1. We found that deletion of Dlgh-1 caused open eyelids, open neural tube, and misorientation of cochlear hair cell stereociliary bundles, indicative of defects in planar cell polarity (PCP). Deletion of Dlgh-1 also caused skeletal defects throughout the embryo. These findings identify novel roles for Dlgh-1 in vertebrates that differ from its well-characterized roles in invertebrates and suggest that the Dlgh-1 null mouse may be a useful animal model to study certain human congenital birth defects. 相似文献
136.
Meetali Singh Maxime Chazal Piergiuseppe Quarato Loan Bourdon Christophe Malabat Thomas Vallet Marco Vignuzzi Sylvie van der Werf Sylvie Behillil Flora Donati Nathalie Sauvonnet Giulia Nigro Maryline Bourgine Nolwenn Jouvenet Germano Cecere 《EMBO reports》2022,23(2)
SARS‐CoV‐2 infection results in impaired interferon response in patients with severe COVID‐19. However, how SARS‐CoV‐2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS‐CoV‐2‐infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus‐derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer, which are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3′UTR of interferon‐stimulated genes and represses their expression in a miRNA‐like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID‐19 patients. We propose that SARS‐CoV‐2 can potentially employ a virus‐derived miRNA to hijack the host miRNA machinery, which could help to evade the interferon‐mediated immune response. 相似文献
137.
Construction of an integration vector for use in the archaebacterium Methanococcus voltae and expression of a eubacterial resistance gene 总被引:8,自引:0,他引:8
Petra Gernhardt Odile Possot Maryline Foglino Lionel Sibold Albrecht Klein 《Molecular & general genetics : MGG》1990,221(2):273-279
Summary An integration vector for use in Methanococcus voltae was constructed, based on the Escherichia coli vector pUC18. It carries the structural gene for puromycin transacetylase from Streptomyces alboniger, which is flanked by expression signals of M. voltae structural genes and hisA gene sequences of this bacterium. Transformed M. voltae cells are puromycin resistant. Several types of integration of the vector into the chromosome were found. Only one case was due to nonhomologous recombination. The integrated sequences were stable under selective pressure but were slowly lost in some cases in the absence of the selective drug. The vector could be excised from M. voltae chromosomal DNA, recircularized and transformed back into E. coli.The order of the other authors is not indicative of the relative importance of their experimental contributions which are considered to be equivalentWe mourn the loss of our colleague and friend Lionel Sibold, who died while this work was still in progress 相似文献
138.
Mark Williams Alan M. Haywood Maryline Vautravers Claus-Dieter Hillenbrand C. Giles Miller 《Geobios》2007,40(6):861
This paper explores the effects of preservation and taphonomy on the ultrastructure of recent and fossil (Quaternary and Neogene) Globigerinoides using scanning electron microscopy and thin section petrography. We show preservation states from: pristine (plankton tow) specimens that are “glassy”, have a microcrystalline test structure, and bear sharply defined interpore ridges with delicate spines; through core top and fossil specimens that have gametogenic calcite veneers of euhedral or lumpy deposits covering the interpore ridges and spine bases; to fossil material with extensive dissolution of the test wall and diagenetic calcite formed during shallow burial (less than 300 m below the sea floor). The latter produce a “grainy” texture to the test. Although we cannot unravel the precise effects of ecology and taphonomy on calcification temperature at every site, we show that for well-preserved fossil material with gametogenic calcite, temperature estimates are typically 2-3 °C cooler than modern sea surface, and are similar to those recorded using the δ18O of core top material from tropical latitudes. In contrast, at tropical sites with poor fossil preservation, estimates of calcification temperature are significantly cooler, sometimes by more than 10 °C than expected from present observations. 相似文献
139.
Outer hair cells (OHCs) provide amplification in the mammalian cochlea using somatic force generation underpinned by voltage-dependent conformational changes of the motor protein prestin. However, prestin must be gated by changes in membrane potential on a cycle-by-cycle basis and the periodic component of the receptor potential may be greatly attenuated by low-pass filtering due to the OHC time constant (τ(m)), questioning the functional relevance of this mechanism. Here, we measured τ(m) from OHCs with a range of characteristic frequencies (CF) and found that, at physiological endolymphatic calcium concentrations, approximately half of the mechanotransducer (MT) channels are opened at rest, depolarizing the membrane potential to near -40 mV. The depolarized resting potential activates a voltage-dependent K+ conductance, thus minimizing τ(m) and expanding the membrane filter so there is little receptor potential attenuation at the cell's CF. These data suggest that minimal τ(m) filtering in vivo ensures optimal activation of prestin. 相似文献
140.