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101.
Amina Bakhchane Majida Charif Sara Salime Redouane Boulouiz Halima Nahili Rachida Roky Guy Lenaers Abdelhamid Barakat 《PloS one》2015,10(9)
Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts. 相似文献
102.
Sherif H. Elmeligy Abdelhamid Chris J. Kuhlman Madhav V. Marathe Henning S. Mortveit S. S. Ravi 《PloS one》2015,10(8)
Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools. 相似文献
103.
The globus pallidus (GP) receives dopaminergic afferents from the pars compacta of substantia nigra and several studies suggested that dopamine exerts its action in the GP through presynaptic D2 receptors (D2Rs). However, the impact of dopamine in GP on the pallido-subthalamic and pallido-nigral neurotransmission is not known. Here, we investigated the role of dopamine, through activation of D2Rs, in the modulation of GP neuronal activity and its impact on the electrical activity of subthalamic nucleus (STN) and substantia nigra reticulata (SNr) neurons. Extracellular recordings combined with local intracerebral microinjection of drugs were done in male Sprague-Dawley rats under urethane anesthesia. We showed that dopamine, when injected locally, increased the firing rate of the majority of neurons in the GP. This increase of the firing rate was mimicked by quinpirole, a D2R agonist, and prevented by sulpiride, a D2R antagonist. In parallel, the injection of dopamine, as well as quinpirole, in the GP reduced the firing rate of majority of STN and SNr neurons. However, neither dopamine nor quinpirole changed the tonic discharge pattern of GP, STN and SNr neurons. Our results are the first to demonstrate that dopamine through activation of D2Rs located in the GP plays an important role in the modulation of GP-STN and GP-SNr neurotransmission and consequently controls STN and SNr neuronal firing. Moreover, we provide evidence that dopamine modulate the firing rate but not the pattern of GP neurons, which in turn control the firing rate, but not the pattern of STN and SNr neurons. 相似文献
104.
Through monthly samplings of grasshoppers taken from five sites in oases and two in steppes in the area of Biskra, 45 species could be recorded. Four assemblages of species can be defined, two in the oasian zones, one in the stony steppe and a last one in the sandy steppe. The two oasian assemblages are interpreted in the light of a gradient of salinity and humidity determined by the vegetation. In each type of steppe, there is a spring sub-assemblage and a summer-autumnal one, but such a distinction is not possible in the anthropised sites. The steppe stations are moreover characterized by a larger diversity determined by the Shannon index and a weaker density than in the oases, in spite of a comparable richness. The comparative analysis of species phenology between the different assemblages allows discussing their adaptation toward seasonal variations of dryness in these arid environments. 相似文献
105.
Eloualid A Abidi O Charif M El Houate B Benrahma H Louanjli N Chadli E Ajjemami M Barakat A Bashamboo A McElreavey K Rhaissi H Rouba H 《PloS one》2012,7(3):e34111
The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants. 相似文献
106.
Majida Charif Safaa Bounaceur Omar Abidi Halima Nahili Hassan Rouba Mostafa Kandil Redouane Boulouiz Abdelhamid Barakat 《Molecular biology reports》2012,39(12):11011-11016
Congenital hearing impairment (HI) affects one in 1,000 newborns and has a genetic cause in 50?% of the cases. Autosomal recessive non-syndromic hearing impairment is responsible for 70–80?% of all hereditary cases of HI. Recently, it has been demonstrated that, mutations of LRTOMT are associated with profound nonsyndromic hearing impairment at the DFNB63 locus. The objective of this study is to evaluate the carrier frequency of c.242G>A mutation in LRTOMT gene and define the contribution of this gene in the etiology of deafness in Moroccan population. We screened 105 unrelated Moroccan families with non-syndromic HI and 120 control individuals for mutation in the exon 8 of the LRTOMT gene, by sequencing and PCR-RFLP. The Homozygous c.242G>A mutation was found in 8.75?% of the families tested and in 4.16?% of control in the heterozygous state. Our results show that after the GJB2 gene mutation in LRTOMT gene is the second cause of congenital hearing impairment in Moroccan patients. This finding should facilitate diagnosis of congenital deafness of the affected subjects in Morocco. 相似文献
107.
A Mutation in PNPT1, Encoding Mitochondrial-RNA-Import Protein PNPase,Causes Hereditary Hearing Loss
Simon von?Ameln Geng Wang Redouane Boulouiz Mark?A. Rutherford Geoffrey?M. Smith Yun Li Hans-Martin Pogoda Gudrun Nürnberg Barbara Stiller Alexander?E. Volk Guntram Borck Jason?S. Hong Richard?J. Goodyear Omar Abidi Peter Nürnberg Kay Hofmann Guy?P. Richardson Matthias Hammerschmidt Tobias Moser Bernd Wollnik Carla?M. Koehler Michael?A. Teitell Abdelhamid Barakat Christian Kubisch 《American journal of human genetics》2012,91(5):919-927
108.
Jonathan Chetrit Bérangère Ballion Steeve Laquitaine Pauline Belujon Stéphanie Morin Anne Taupignon Bernard Bioulac Christian E. Gross Abdelhamid Benazzouz 《PloS one》2009,4(7)
Background
Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, α-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat.Methods and Findings
The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that α-flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, α-flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by α-flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by α-flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, α-flupentixol failed to induce EPS and to alter STN neuronal activity.Conclusion
Our study reports strong evidence to show that hypokinesia and catalepsy induced by α-flupentixol are triggered by dramatic changes occurring in basal ganglia network. We provide new insight into the key role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can be considered as a potential target for the treatment of EPS. 相似文献109.
Almolki A Taillé C Martin GF Jose PJ Zedda C Conti M Megret J Henin D Aubier M Boczkowski J 《American journal of physiology. Lung cellular and molecular physiology》2004,287(1):L26-L34
Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PGE(2), and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg i.p.) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 micromol/kg i.p.). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs. 相似文献
110.
Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes 总被引:8,自引:0,他引:8
Liacini A Sylvester J Zafarullah M 《Biochemical and biophysical research communications》2005,327(1):320-327
A hallmark of rheumatoid- and osteoarthritis (OA) is proinflammatory cytokine-induced degeneration of cartilage collagen and aggrecan by matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS). Effects of the Chinese herb, Tripterygium wilfordii Hook F (TWHF), on cartilage and its anti-arthritic mechanisms are poorly understood. This study investigated the impact of a purified derivative of TWHF, PG490 (triptolide), on cytokine-stimulated expression of the major cartilage damaging proteases, MMP-3, MMP-13, and ADAMTS4. PG490 inhibited cytokine-induced MMP-3, MMP-13 gene expression in primary human OA chondrocytes, bovine chondrocytes, SW1353 cells, and human synovial fibroblasts. Triptolide was effective at low doses and blocked the induction of MMP-13 by IL-1 in human and bovine cartilage explants. TWHF extract and PG490 also suppressed IL-1-, IL-17-, and TNF-alpha-induced expression of ADAMTS-4 in bovine chondrocytes. Thus, PG490 could protect cartilage from MMP- and aggrecanase-driven breakdown. The immunosuppressive, cartilage protective, and anti-inflammatory properties could make PG490 potentially a new therapeutic agent for arthritis. 相似文献