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91.
Mahfouz RA Sarieddine DS Charafeddine KM Abdul Khalik RN Cortas NK Daher RT 《Molecular biology reports》2012,39(1):753-759
Hereditary hemochromatosis (HHC) is a genetic disorder of iron metabolism characterized by abnormal accumulation of iron that
may lead to organ damage and death. Diagnosis is usually based on various genetic and phenotypic criteria. The study goals
were to perform mutation analysis for 18 different mutations associated with HHC in healthy Lebanese, determine their allele
frequency, and compare iron-overload status in identified carriers versus those found to be wild-type for mutations analyzed.
116 healthy adults (59 males and 57 females) underwent DNA testing for 18 different HHC mutations, and biochemical testing
for percent transferrin saturation (%TS) and ferritin. C282Y mutation was not detected. Only H63D mutation (rs1799945) was
found with an overall carrier frequency of 25.8% (24.1% heterozygous and 1.7% homozygous). %TS and ferritin differed significantly
between genders. %TS and ferritin were significantly higher in males with H63D mutation when compared to males with wild-type
(P = 0.001, 0.019; respectively); but not in females. The proportion of subjects with increased %TS and serum ferritin was not
statistically different between those with H63D mutation and the wild-type in either gender. In addition, none of the subjects
had concurrent increase in %TS and ferritin. In conclusion, the H63D carrier frequency in healthy Lebanese is comparable to
other populations in the region, and it does not result in significant biochemical iron overload. Moreover, in the absence
of the C282Y mutation, genetic screening for HHC is not recommended according to this preliminary study in healthy Lebanese. 相似文献
92.
Marije Oosting Kathrin Buffen Subbarao RK Malireddi Patrick Sturm Ineke Verschueren Marije I Koenders Frank L van de Veerdonk Jos WM van der Meer Mihai G Netea Thirumala-Devi Kanneganti Leo AB Joosten 《Arthritis research & therapy》2012,14(6):R247
Introduction
The protein platform called the NOD-like-receptor -family member (NLRP)-3 inflammasome needs to be activated to process intracellular caspase-1. Active caspase-1 is able to cleave pro-Interleukin (IL)-1β, resulting in bioactive IL-1β. IL-1β is a potent proinflammatory cytokine, and thought to play a key role in the pathogenesis of Lyme arthritis, a common manifestation of Borrelia burgdorferi infection. The precise pathways through which B. burgdorferi recognition leads to inflammasome activation and processing of IL-1β in Lyme arthritis has not been elucidated. In the present study, we investigated the contribution of several pattern recognition receptors and inflammasome components in a novel murine model of Lyme arthritis.Methods
Lyme arthritis was elicited by live B. burgdorferi, injected intra-articularly in knee joints of mice. To identify the relevant pathway components, the model was applied to wild-type, NLRP3-/-, ASC-/-, caspase-1-/-, NOD1-/-, NOD2-/-, and RICK-/- mice. As a control, TLR2-/-, Myd88-/- and IL-1R-/- mice were used. Peritoneal macrophages and bone marrow-derived macrophages were used for in vitro cytokine production and inflammasome activation studies. Joint inflammation was analyzed in synovial specimens and whole knee joints. Mann-Whitney U tests were used to detect statistical differences.Results
We demonstrate that ASC/caspase-1-driven IL-1β is crucial for induction of B. burgdorferi-induced murine Lyme arthritis. In addition, we show that B. burgdorferi-induced murine Lyme arthritis is less dependent on NOD1/NOD2/RICK pathways while the TLR2-MyD88 pathway is crucial.Conclusions
Murine Lyme arthritis is strongly dependent on IL-1 production, and B. burgdorferi induces inflammasome-mediated caspase-1 activation. Next to that, murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and RICK independent. Also, caspase-1 activation by B. burgdorferi is dependent on TLR2 and MyD88. Based on present results indicating that IL-1 is one of the major mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL-1 activity may also have beneficial effects in chronic Lyme arthritis. 相似文献93.
94.
95.
One of the rare weak points of the model plant Arabidopsis is the technical problem associated with the germination of its male gametophyte and the generation of the pollen tube in
vitro. Arabidopsis pollen being tricellular has a notoriously low in vitro germination compared to species with bicellular pollen. This drawback
strongly affects the reproducibility of experiments based on this cellular system. Together with the fact that pollen collection
from this species is tedious, these are obstacles for the standard use of Arabidopsis pollen for experiments that require high numbers of pollen tubes and for which the percentage of germination needs to be
highly reproducible. The possibility of freeze-storing pollen after bulk collection is a potential way to solve these problems,
but necessitates methods that ensure continued viability and reproducible capacity to germinate. Our objective was the optimization
of germination conditions for Arabidopsis pollen that had been freeze-stored. We optimized the concentrations of various media components conventionally used for in
vitro pollen germination. We found that in general 4 mM calcium, 1.62 mM boric acid, 1 mM potassium, 1 mM magnesium, 18% sucrose
at pH 7 and a temperature of 22.5°C are required for optimal pollen germination. However, different experimental setups may
deviate in their requirements from this general protocol. We suggest how to optimally use these optimized methods for different
practical experiments ranging from morphological observations of pollen tubes in optical and electron microscopy to their
bulk use for molecular and biochemical analyses or for experimental setups for which a specific medium stiffness is critical.
F. Bou Daher and Y. Chebli contributed equally to this study. 相似文献
96.
Background
Previously it has been shown that insulin-mediated tyrosine phosphorylation of myosin heavy chain is concomitant with enhanced association of C-terminal SRC kinase during skeletal muscle differentiation. We sought to identify putative site(s) for this phosphorylation event. 相似文献97.
Changes in plastid proteome and structure in arbuscular mycorrhizal roots display a nutrient starvation signature
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Zeina Daher Ghislaine Recorbet Katalin Solymosi Stefanie Wienkoop Arnaud Mounier Dominique Morandi Jeannine Lherminier Daniel Wipf Eliane Dumas‐Gaudot Benoît Schoefs 《Physiologia plantarum》2017,159(1):13-29
During arbuscular mycorrhizal symbiosis, arbuscule‐containing root cortex cells display a proliferation of plastids, a feature usually ascribed to an increased plant anabolism despite the lack of studies focusing on purified root plastids. In this study, we investigated mycorrhiza‐induced changes in plastidic pathways by performing a label‐free comparative subcellular quantitative proteomic analysis targeted on plastid‐enriched fractions isolated from Medicago truncatula roots, coupled to a cytological analysis of plastid structure. We identified 490 root plastid protein candidates, among which 79 changed in abundance upon mycorrhization, as inferred from spectral counting. According to cross‐species sequence homology searches, the mycorrhiza‐responsive proteome was enriched in proteins experimentally localized in thylakoids, whereas it was depleted of proteins ascribed predominantly to amyloplasts. Consistently, the analysis of plastid morphology using transmission electron microscopy indicated that starch depletion associated with the proliferation of membrane‐free and tubular membrane‐containing plastids was a feature specific to arbusculated cells. The loss of enzymes involved in carbon/nitrogen assimilation and provision of reducing power, coupled to macromolecule degradation events in the plastid‐enriched fraction of mycorrhizal roots that paralleled lack of starch accumulation in arbusculated cells, lead us to propose that arbuscule functioning elicits a nutrient starvation and an oxidative stress signature that may prime arbuscule breakdown. 相似文献
98.
Small interfering RNAs against the TAR RNA binding protein, TRBP, a Dicer cofactor, inhibit human immunodeficiency virus type 1 long terminal repeat expression and viral production
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Christensen HS Daher A Soye KJ Frankel LB Alexander MR Lainé S Bannwarth S Ong CL Chung SW Campbell SM Purcell DF Gatignol A 《Journal of virology》2007,81(10):5121-5131
RNA interference (RNAi) is now widely used for gene silencing in mammalian cells. The mechanism uses the RNA-induced silencing complex, in which Dicer, Ago2, and the human immunodeficiency virus type 1 (HIV-1) TAR RNA binding protein (TRBP) are the main components. TRBP is a protein that increases HIV-1 expression and replication by inhibition of the interferon-induced protein kinase PKR and by increasing translation of viral mRNA. After HIV infection, TRBP could restrict the viral RNA through its activity in RNAi or could contribute more to the enhancement of viral replication. To determine which function will be predominant in the virological context, we analyzed whether the inhibition of its expression could enhance or decrease HIV replication. We have generated small interfering RNAs (siRNAs) against TRBP and found that they decrease HIV-1 long terminal repeat (LTR) basal expression 2-fold, and the LTR Tat transactivated level up to 10-fold. In the context of HIV replication, siRNAs against TRBP decrease the expression of viral genes and inhibit viral production up to fivefold. The moderate increase in PKR expression and activation indicates that it contributes partially to viral gene inhibition. The moderate decrease in micro-RNA (miRNA) biogenesis by TRBP siRNAs suggests that in the context of HIV replication, TRBP functions other than RNAi are predominant. In addition, siRNAs against Dicer decrease viral production twofold and impede miRNA biogenesis. These results suggest that, in the context of HIV replication, TRBP contributes mainly to the enhancement of virus production and that Dicer does not mediate HIV restriction by RNAi. 相似文献
99.
Macrophages (Mφs) play a crucial role in the development of atherosclerosis by engulfing modified LDL particles and forming foam cells, the hallmark of atherosclerosis. Many studies suggest that myeloperoxidase-oxidized LDL (Mox-LDL) is an important pathophysiological model for LDL modification in vivo. Classically (M1) and alternatively activated (M2) Mφs are both implicated in the process of atherogenesis. Mφs are highly plastic cells whereby they undergo repolarization from M1 to M2 and vice versa. Since little is known about the effects of Mox-LDL on Mφ polarization and repolarization, our study aimed at evaluating the in vitro effects of Mox-LDL at this level through making use of the well-established model of human THP-1-derived Mφs. Resting M0-Mφs were polarized toward M1- and M2-Mφs, then M0-, M1- and M2-Mφs were all treated with physiological concentrations of Mox-LDL to assess the effect of Mox-LDL treatment on Mφ polarization and repolarization. Treatment of M0-Mφs with a physiological concentration of Mox-LDL had no significant effects at the level of their polarization. However, treatment of M1-Mφs with Mox-LDL resulted in a significant reduction in their IL-10 cytokine secretion. Our results point to a potential role of Mox-LDL in increasing the pro-inflammatory state in Mφs through reducing the release of the anti-inflammatory cytokine, IL-10. 相似文献
100.