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111.
The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains
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J. D. Eicher C. M. Stein F. Deng A. A. Ciesla N. R. Powers R. Boada S. D. Smith B. F. Pennington S. K. Iyengar B. A. Lewis J. R. Gruen 《Genes, Brain & Behavior》2015,14(4):377-385
A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples – Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) – and then combined results by meta‐analysis. DYX2 markers, specifically those in the 3′ untranslated region of DCDC2 (P = 1.43 × 10?4), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic‐related genes ANKK1 (P = 1.02 × 10?2) and DRD2 (P = 9.22 × 10?3) and nicotinic‐related genes CHRNA3 (P = 2.51 × 10?3) and BDNF (P = 8.14 × 10?3) with case–control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language‐related outcomes remains to be elucidated. 相似文献
112.
Irene EM Bultink D?rte Hamann Marc A Seelen Margreet H Hart Ben AC Dijkmans Mohamed R Daha Alexandre E Voskuyl 《Arthritis research & therapy》2007,8(6):R183
Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE
patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has
also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for
mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with
patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional
MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship
with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with
SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan
as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using
an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected
with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented
infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous
administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented
in the 103 SLE patients (mean age 41 ± 13 years, mean disease duration 7 ± 4 years). The percentage of SLE patients with severe
MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan
and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels
nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients
frequently suffer from infections, but deficiency of functional MBL does not confer additional risk. 相似文献
113.
114.
Oxidation of Dimethyl Sulfide to Dimethyl Sulfoxide by Phototrophic Purple Bacteria 总被引:1,自引:5,他引:1
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Josef Zeyer Petra Eicher Stuart G. Wakeham Ren P. Schwarzenbach 《Applied microbiology》1987,53(9):2026-2032
Enrichment cultures of phototrophic purple bacteria rapidly oxidized up to 10 mM dimethyl sulfide (DMS) to dimethyl sulfoxide (DMSO). DMSO was qualitatively identified by proton nuclear magnetic resonance. By using a biological assay, DMSO was always quantitatively recovered from the culture media. DMS oxidation was not detected in cultures incubated in the dark, and it was slow in cultures exposed to full daylight. Under optimal conditions, the second-order rate constant for DMS oxidation was 6 day−1 mg of protein−1 ml−1. The rate constant was reduced in the presence of high concentration of sulfide (>1 mM), but was not affected by the addition of acetate. DMS was also oxidized to DMSO by a pure strain (tentatively identified as a Thiocystis sp.) isolated from the enrichment cultures. DMS supported growth of the enrichment cultures and of the pure strain by serving as an electron source for photosynthesis. A determination of the amount of protein produced in the cultures and an estimation of the electron balance suggested that the two electrons liberated during the oxidation of DMS to DMSO were quantitatively used to reduce carbon dioxide to biomass. The oxidation of DMS by phototrophic purple bacteria may be an important source of DMSO detected in anaerobic ponds and marshes. 相似文献
115.
116.
Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development 总被引:9,自引:0,他引:9
Examination of 18 complete and 6 partial sequences of the major outer-
membrane protein from 24 chlamydiae isolates was used to reconstruct their
evolutionary relationships. From this analysis, assuming that the clades
with 100% bootstrap support are correct, come the following conclusions:
(1) The tree of these sequences is not congruent with the phylogeny of the
hosts, and thus host switching would seem to have occurred, thereby
limiting the extent to which there has been coevolution of parasite and
host. (2) The tree is also noncongruent with clustering by type of cell
infected, thereby limiting the extent to which there has been coevolution
of parasite and the cell type that it infects. (3) The tree is also
noncongruent with clustering by the organ infected (eyes or genitalia),
thereby limiting the extent to which there has been coevolution of parasite
and the organ that it infects. (4) The tree is also noncongruent with
genital strains arising from lymphogranuloma venereum strains. (5) The tree
is also noncongruent with the geographic site at which the isolates were
obtained, thereby limiting the extent of divergence explained by geographic
separation. (6) There are estimated to be 185 amino acid positions that are
invariable (as opposed to unvaried) in the major outer-membrane protein.
There are 10 unvaried positions in the variable domains, of which 9 appear
to be invariable, giving some reason to hope that development of a vaccine
might be possible. (7) The rate of change of this protein is too small to
see increased divergence over the time span of isolation of these genes,
giving hope to any vaccine having longevity. Bootstrapping supports those
portions of the tree on which the first five conclusions above depend. The
picture that these results provide is more one of pathogen versatility than
one of coevolutionary constraints. In addition, we examined 10 60-KDa,
outer-membrane protein- 2 genes, all but one of which were from these same
strains. The tree was not, among the trachomatis strains, congruent with
the major-outer- membrane protein tree, suggesting that gene exchange could
be occurring among strains. Moreover, there is an apparent slowdown in
divergence in this gene, among the trachomatis strains.
相似文献
117.
Angelika Wientzek María‐José Tormo Díaz Jose Maria Huerta Castaño Pilar Amiano Larraitz Arriola Kim Overvad Jane Nautrup Østergaard Marie‐Aline Charles Guy Fagherazzi Domenico Palli Benedetta Bendinelli Guri Skeie Kristin Benjaminsen Borch Wanda Wendel‐Vos Ellen de Hollander Anne M. May Marjolein EM den Ouden Antonia Trichopoulou Elissavet Valanou Stefan Söderberg Paul W. Franks Soren Brage Matthäus Vigl Heiner Boeing Ulf Ekelund 《Obesity (Silver Spring, Md.)》2014,22(5):E127-E134
118.
119.
Steenvoorden MM Tolboom TC van der Pluijm G Löwik C Visser CP DeGroot J Gittenberger-DeGroot AC DeRuiter MC Wisse BJ Huizinga TW Toes RE 《Arthritis research & therapy》2006,8(6):R165-10
The healthy synovial lining layer consists of a single cell layer that regulates the transport between the joint cavity and the surrounding tissue. It has been suggested that abnormalities such as somatic mutations in the p53 tumor-suppressor gene contribute to synovial hyperplasia and invasion in rheumatoid arthritis (RA). In this study, expression of epithelial markers on healthy and diseased synovial lining tissue was examined. In addition, we investigated whether a regulated process, resembling epithelial to mesenchymal transition (EMT)/fibrosis, could be responsible for the altered phenotype of the synovial lining layer in RA. Synovial tissue from healthy subjects and RA patients was obtained during arthroscopy. To detect signs of EMT, expression of E-cadherin (epithelial marker), collagen type IV (indicator of the presence of a basement membrane) and alpha-smooth muscle actin (alpha-sma; a myofibroblast marker) was investigated on frozen tissue sections using immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from healthy subjects were isolated and subjected to stimulation with synovial fluid (SF) from two RA patients and to transforming growth factor (TGF)-beta. To detect whether EMT/fibrotic markers were increased, expression of collagen type I, alpha-sma and telopeptide lysylhydroxylase (TLH) was measured by real time PCR. Expression of E-cadherin and collagen type IV was found in healthy and arthritic synovial tissue. Expression of alpha-sma was only found in the synovial lining layer of RA patients. Stimulation of healthy FLSs with SF resulted in an upregulation of alpha-sma and TLH mRNA. Collagen type I and TLH mRNA were upregulated after stimulation with TGF-beta. Addition of bone morphogenetic protein (BMP)-7 to healthy FLS stimulated with SF inhibited the expression of alpha-sma mRNA. The finding that E-cadherin and collagen type IV are expressed in the lining layer of healthy and arthritic synovium indicates that these lining cells display an epithelial-like phenotype. In addition, the presence of alpha-sma in the synovial lining layer of RA patients and induction of fibrotic markers in healthy FLSs by SF from RA patients indicate that a regulated process comparable to EMT might cause the alteration in phenotype of RA FLSs. Therefore, BMP-7 may represent a promising agent to counteract the transition imposed on synoviocytes in the RA joint. 相似文献
120.