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Alexandra Laberge Akram Ayoub Syrine Arif Sébastien Larochelle Alain Garnier Véronique J. Moulin 《Journal of cellular physiology》2019,234(7):11369-11379
Microvesicles (MVs) are recognized as an important class of cell-to-cell messengers. Although the properties of MVs are increasingly documented, the mechanisms regulating MV biogenesis remain debated. Myofibroblasts are a key cellular component of wound healing and have been shown to produce MVs upon stimulation with serum. However, the mediator(s) responsible for the observed effect of serum on MV release have yet to be identified. To isolate the molecule(s) of interest, serum proteins were sequentially separated using chromatography, selective precipitation, and electrophoresis. MV production was assessed throughout the purification and after stimulation of myofibroblasts with two potent purified molecules. α-2-Macroglobulin (A2M) was thereby found to dose-dependently stimulate MV release. We confirmed the presence of the A2M receptor, low-density lipoprotein receptor-related protein-1 (LRP1), on myofibroblasts. Inhibition of LRP1 resulted in a significant decrease in MV production. Together, our results suggest that A2M positively regulates MV shedding through the activation of LRP1 on myofibroblasts. 相似文献
54.
Ilanchezhian Shanmugam Mohammad Abbas Farhan Ayoub Susan Mirabal Manal Bsaili Erin K. Caulder David M. Weinstock Alan E. Tomkinson Robert Hromas Monte Shaheen 《The Journal of biological chemistry》2014,289(33):22739-22748
Rad17 is a subunit of the Rad9-Hus1-Rad1 clamp loader complex, which is required for Chk1 activation after DNA damage. Rad17 has been shown to be regulated by the ubiquitin-proteasome system. We have identified a deubiquitylase, USP20 that is required for Rad17 protein stability in the steady-state and post DNA damage. We demonstrate that USP20 and Rad17 interact, and that this interaction is enhanced by UV exposure. We show that USP20 regulation of Rad17 is at the protein level in a proteasome-dependent manner. USP20 depletion results in poor activation of Chk1 protein by phosphorylation, consistent with Rad17 role in ATR-mediated phosphorylation of Chk1. Similar to other DNA repair proteins, USP20 is phosphorylated post DNA damage, and its depletion sensitizes cancer cells to damaging agents that form blocks ahead of the replication forks. Similar to Chk1 and Rad17, which enhance recombinational repair of collapsed replication forks, we demonstrate that USP20 depletion impairs DNA double strand break repair by homologous recombination. Together, our data establish a new function of USP20 in genome maintenance and DNA repair. 相似文献
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Muhammad Zoabi Prathamesh T. Nadar-Ponniah Hanan Khoury-Haddad Marko Usaj Inbal Budowski-Tal Tali Haran Arnon Henn Yael Mandel-Gutfreund Nabieh Ayoub 《Nucleic acids research》2014,42(21):13026-13038
The JmjC-containing lysine demethylase, KDM4D, demethylates di-and tri-methylation of histone H3 on lysine 9 (H3K9me3). How KDM4D is recruited to chromatin and recognizes its histone substrates remains unknown. Here, we show that KDM4D binds RNA independently of its demethylase activity. We mapped two non-canonical RNA binding domains: the first is within the N-terminal spanning amino acids 115 to 236, and the second is within the C-terminal spanning amino acids 348 to 523 of KDM4D. We also demonstrate that RNA interactions with KDM4D N-terminal region are critical for its association with chromatin and subsequently for demethylating H3K9me3 in cells. This study implicates, for the first time, RNA molecules in regulating the levels of H3K9 methylation by affecting KDM4D association with chromatin. 相似文献
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S. Kathleen Bandt David T. Bundy Ammar H. Hawasli Kareem W. Ayoub Mohit Sharma Carl D. Hacker Mrinal Pahwa Eric C. Leuthardt 《PloS one》2014,9(9)
Objective
The role of resting state functional networks in epilepsy is incompletely understood. While some pathologic diagnoses have been shown to have maintained but altered resting state connectivity, others have implicated resting state connectivity in disease progression. However little is known about how these resting state networks influence the behavior of a focal neocortical seizure.Methods
Using data taken from invasively monitored patients with intractable focal neocortical epilepsy, we evaluated network connectivity (as determined by oscillatory covariance of the slow cortical potential (<0.5 Hz)) as it relates to neocortical seizure foci both in the interictal and ictal states.Results
Similar to what has been shown in the past for sleep and anesthesia, electophysiologic resting state networks that are defined by this slow cortical potential covariance maintain their topographic correlation structure throughout an ictal event. Moreover, in the context of focal epilepsy in which the seizure has a specific site of onset, seizure propagation is not chaotic or random. Rather, the seizure (reflected by an elevation of high frequency power) preferentially propagates along the network that contains the seizure onset zone.Significance
Taken together, these findings further undergird the fundamental role of resting state networks, provide novel insights into the network-influenced behavior of seizures, and potentially identify additional targets for surgical disconnection including informing the location for the completion of multiple subpial transections (MSPTs). 相似文献57.
Purpose
Superimposition of two dimensional preoperative and postoperative facial images, including radiographs and photographs, are used to evaluate the surgical changes after orthognathic surgery. Recently, three dimensional (3D) imaging has been introduced allowing more accurate analysis of surgical changes. Surface based registration and voxel based registration are commonly used methods for 3D superimposition. The aim of this study was to evaluate and compare the accuracy of the two methods.Materials and methods
Pre-operative and 6 months post-operative cone beam CT scan (CBCT) images of 31 patients were randomly selected from the orthognathic patient database at the Dental Hospital and School, University of Glasgow, UK. Voxel based registration was performed on the DICOM images (Digital Imaging Communication in Medicine) using Maxilim software (Medicim-Medical Image Computing, Belgium). Surface based registration was performed on the soft and hard tissue 3D models using VRMesh (VirtualGrid, Bellevue City, WA). The accuracy of the superimposition was evaluated by measuring the mean value of the absolute distance between the two 3D image surfaces. The results were statistically analysed using a paired Student t-test, ANOVA with post-hoc Duncan test, a one sample t-test and Pearson correlation coefficient test.Results
The results showed no significant statistical difference between the two superimposition methods (p<0.05). However surface based registration showed a high variability in the mean distances between the corresponding surfaces compared to voxel based registration, especially for soft tissue. Within each method there was a significant difference between superimposition of the soft and hard tissue models.Conclusions
There were no significant statistical differences between the two registration methods and it was unlikely to have any clinical significance. Voxel based registration was associated with less variability. Registering on the soft tissue in isolation from the hard tissue may not be a true reflection of the surgical change. 相似文献58.
Benesch JL Ayoub M Robinson CV Aquilina JA 《The Journal of biological chemistry》2008,283(42):28513-28517
The alpha-crystallins are members of the small heat shock protein family of molecular chaperones that have evolved to minimize intracellular protein aggregation; however, they are also implicated in a number of protein deposition diseases. In this study, we employed novel mass spectrometry techniques to investigate the changes in quaternary structure associated with this switch from chaperone to adjuvant of aggregation. We replicated the oligomeric rearrangements observed for post-translationally modified alpha-crystallins, without altering the protein sequence, by refolding the alpha-crystallins in vitro. This refolding resulted in a loss of dimeric substructure concomitant with an augmentation of substrate affinity. We show that packaging of small heat shock proteins into dimeric units is used to control the level of chaperone function by regulating the exposure of hydrophobic surfaces. We propose that a bias toward monomeric substructure is responsible for the aberrant chaperone behavior associated with the alpha-crystallins in protein deposition diseases. 相似文献
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Safa Jammali Esaie Kuitche Ayoub Rachati François Bélanger Michelle Scott Aïda Ouangraoua 《Algorithms for molecular biology : AMB》2017,12(1):10