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排序方式: 共有273条查询结果,搜索用时 15 毫秒
41.
Ebru Ercan Sameh Eid Christian Weber Alexandra Kowalski Maria Bichmann Annika Behrendt Frank Matthes Sybille Krauss Peter Reinhardt Simone Fulle Dagmar E. Ehrnhoefer 《Molecular neurodegeneration》2017,12(1):87
Background
Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer’s disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used. However, quality control of these antibodies is lacking and their specificity for particular modifications is often unclear.Methods
In this study, we first designed an online tool called ‘TauPTM’, which enables the visualization of PTMs and their interactions on human tau. Using TauPTM, we next searched for commercially available antibodies against tau PTMs and characterized their specificity by peptide array, immunoblotting, electrochemiluminescence ELISA and immunofluorescence technologies.Results
We demonstrate that commercially available antibodies can show a significant lack of specificity, and PTM-specific antibodies in particular often recognize non-modified versions of the protein. In addition, detection may be hindered by other PTMs in close vicinity, complicating the interpretation of results. Finally, we compiled a panel of specific antibodies and show that they are useful to detect PTM-modified endogenous tau in hiPSC-derived neurons and mouse brains.Conclusion
This study has created a platform to reliably and robustly detect changes in localization and abundance of post-translationally modified tau in health and disease. A web-based version of TauPTM is fully available at http://www.tauptm.org.42.
43.
Amal M. Mohamed Tarek F. Elwakil Ibrahim M. Taher Mohamed M. Elbarbary Hesham F. Kayed Hassan A. Hussein Ola M. Eid 《Cell and tissue research》2009,338(1):107-115
Cyclin D1 gene amplification has been reported to promote abnormal endothelial cell proliferation and angiogenesis; these
findings constantly present in proliferating haemangiomas. The present study was conducted to evaluate cyclin D1 gene amplification
by fluorescence in situ hybridization analysis in tissue biopsies of 22 proliferating haemangiomas from 20 infants. Two significant
correlations of cyclin D1 gene amplification with the early onset and the duplication of proliferating haemangiomas have been
observed. Moreover, a significant correlation (P≤0.05) has been found between the treatment parameters of proliferating haemangiomas with the amplified versus the normal
cyclin D1 gene. Proliferating haemangiomas with the amplified cyclin D1 gene required more frequent flashlamp pulsed dye laser
treatment sessions at the maximum dosimetry and more frequent intralesional steroid injections at the maximum dose/injection
but treatment outcomes were limited. The more frequent post-treatment complications among proliferating haemangiomas with
cyclin D1 gene amplification might be attributable not only to the associated more aggressive natural course, but also to
the higher treatment parameters needed for effective treatment. Within the limitations of the present study, cyclin D1 gene
amplification was seen for the first time in proliferating haemangiomas. We have found that the amplification of the cyclin
D1 gene can predict the more aggressive natural course of proliferating haemangiomas and the limited outcome and higher incidence
of complications after non–excision treatment modalities. The present findings reflect the possible usefulness of antisense
cyclin D1 to improve the therapeutic outcome of proliferating haemangiomas. 相似文献
44.
Chuansheng Niu Diane H. Boschelli L. Nathan Tumey Niala Bhagirath Joan Subrath Jaechul Shim Yan Wang Biqi Wu Clark Eid Julie Lee Xiaoke Yang Agnes Brennan Divya Chaudhary 《Bioorganic & medicinal chemistry letters》2009,19(20):5829-5832
A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCθ inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCθ inhibitor with good selectivity over PKCδ. 相似文献
45.
Physiological functions of beneficial elements 总被引:3,自引:0,他引:3
46.
Gordon W Slysz Charles AH Baker Benjamin M Bozsa Anthony Dang Andrew J Percy Melissa Bennett David C Schriemer 《BMC bioinformatics》2009,10(1):162
Background
Hydrogen/deuterium exchange mass spectrometry (H/DX-MS) experiments implemented to characterize protein interaction and protein folding generate large quantities of data. Organizing, processing and visualizing data requires an automated solution, particularly when accommodating new tandem mass spectrometry modes for H/DX measurement. We sought to develop software that offers flexibility in defining workflows so as to support exploratory treatments of H/DX-MS data, with a particular focus on the analysis of very large protein systems and the mining of tandem mass spectrometry data. 相似文献47.
Monoclonal antibodies (MAbas) constitute remarkable tools to analyze the relationship between the structure and the function of a protein. By immunizing a mouse with a 29mer peptide (K159) formed by residues 147 to 175 of the HIV-1 integrase (IN), we obtained a monoclonal antibody (MAba4) recognizing an epitope lying in the N-terminal portion of K159 (residues 147-166 of IN). The boundaries of the epitope were determined in ELISA assays using peptide truncation and amino acid substitutions. The epitope in K159 or as a free peptide (pep-a4) was mostly a random coil in solution, while in the CCD (catalytic core domain) crystal, the homologous segment displayed an amphipathic helix structure (α4-helix) at the protein surface. Despite this conformational difference, a strong antigenic crossreactivity was observed between pep-a4 and the protein segment, as well as K156, a stabilized analogue of pep-a4 constrained into helix by seven helicogenic mutations, most of them involving hydrophobic residues. We concluded that the epitope is freely accessible to the antibody inside the protein and that its recognition by the antibody is not influenced by the conformation of its backbone and the chemistry of amino acids submitted to helicogenic mutations. In contrast, the AA →Glu mutations of the hydrophilic residues Gln148, Lys156 and Lys159, known for their interactions with LTRs (long terminal repeats) and inhibitors (5CITEP, for instance), significantly impaired the binding of K156 to the antibody. Moreover, we found that in competition ELISAs, the processed and unprocessed LTR oligonucleotides interfered with the binding of MAba4 to IN and K156, confirming that the IN α4-helix uses common residues to interact with the DNA target and the MAba4 antibody. This also explains why, in our standard in vitro concerted integration assays, MAba4 strongly impaired the IN enzymatic activity. 相似文献
48.
Human exposure to metals is of increasing concern due to the well-documented toxic and carcinogenic effects of metals and metal compounds, and the rising environmental levels due to industrial processes and pollution. It has been reported that metals can be genotoxic by several modes of action including generation of reactive oxygen species and inhibition of DNA repair. The aim of this study was to evaluate microsatellite instability (MSI) in three microsatellite loci (D6mit3, D9mit2 and D15Mgh1) located within three common fragile sites in the genome of the laboratory rat (6q21, 9q32-9q33 and 15p14) exposed to acute and chronic doses of a metal salt (lead acetate trihydrate) and a metalloid oxide (arsenic trioxide). In the acute and sub-chronic studies with the two compounds, MSI was observed in the three loci as deletions or additions of microsatellite repeats. The percentages of MSI were 36.4% and 42.1% for lead acetate and arsenic trioxide, respectively. Results of the present work indicate that the microsatellites located within fragile sites provide a convenient assay system to detect changes in DNA sequences resulting from exposure to genotoxic agents. 相似文献
49.
Yusra Al Dhaheri Samir Attoub Gaber Ramadan Kholoud Arafat Khuloud Bajbouj Noushad Karuvantevida Synan AbuQamar Ali Eid Rabah Iratni 《PloS one》2014,9(10)
Background
In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.Results
We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.Conclusion
In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration. 相似文献50.
Sharshar A. A.H Mohamed Shahen Esmat F. Ali Ali Majrashi Eid S.D. M Azza E. Khaffagy Mohamed F. Ageba 《Saudi Journal of Biological Sciences》2022,29(4):3023
Knowledge of soil weed seed bank is important for population dynamics studied, establishment of appropriate weed management programs, a little effort in understanding weed seed bank can give valuable information about what weeds to expect in growing season, weed density, and when most weed germination will take place. In this study, a two - year''s, two sites were carried out with the aim of assessing weed seed bank status of the soil throughout 2018 and 2019. A site was worked out in Sakha Agriculture Research farm act as a clay soil, Kafr El-Sheikh Governorate, Agriculture Research Center (ARC). Another site was worked out in El-Ismailia Agr; Res; farm act as sandy soil, El-Ismailia Governorate, ARC. At each site, soil samples were selected from nine different places as like three Zigzag shapes divided into three, six and nine sites, “W” to act the whole soil area (30 faddan in Sakha farm, and 15 faddan in El-Ismailia farm). The soil samples were taken from topsoil 0–10 cm depth with an auger (core) 10 cm diameter the soils without tillage and before sowing the summer crop. The result of present the study in two different stations and soils, revealed that the number of soil samples to estimate weed seed banks should be either six or nine sites; each sample weighted 0.50 Kg soil with zigzag shape act a direct seed extraction technique to able recognize the abundance of weed species into the soil and their seed density. The aim is to improve integrated weed control. 相似文献