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41.
Thalappilly S Suliman M Gayet O Soubeyran P Hermant A Lecine P Iovanna JL Dusetti NJ 《Proteomics》2008,8(15):3071-3081
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that shows minimal response to chemotherapy. Genetic changes involved in the progression of PDAC concern genes that encode proteins related to signal transduction networks. This fact reveals the importance in identifying the role and the relations between multiple signaling cascades in PDAC. One of the major factors that modulate signaling events is multidomain scaffold proteins that function by binding several proteins simultaneously, inducing their proximity and influencing the outcome of signaling. A particular group among them, containing multiple Src homology 3 (SH3) domains that can bind proteins containing proline-rich motifs, was associated to different aspects of cancer cell homeostasis. In this work, using a microarray-based analysis, we have shown that 13 multiple SH3 domain containing scaffold proteins are expressed in PDAC cells. Using a yeast two-hybrid approach, we have identified proteins that interact with these adaptor proteins. Among them we have found several molecules that modulate cell proliferation and survival (CIZ1, BIRC6, RBBP6), signaling (LTBP4, Notch2, TOM1L1, STK24) and membrane dynamics (PLSCR1, DDEF2, VCP). Our results indicate that interactions mediated by multi-SH3 domain-containing proteins could lead to the formation of dynamic protein complexes that function in pancreatic cancer cell signaling. The identification of such protein complexes is of paramount importance in deciphering pancreatic cancer biology and designing novel therapeutic approaches. 相似文献
42.
Telomeres play the key protective role at chromosomes. Many studies indicate that loss of telomere function causes activation
of DNA damage response. Here, we review evidence supporting interdependence between telomere maintenance and DNA damage response
and present a model in which these two pathways are combined into a single mechanism for protecting chromosomal integrity.
Proteins directly involved in telomere maintenance and DNA damage response include Ku, DNA-PKcs, RAD51D, PARP-2, WRN and RAD50/MRE11/NBS1
complex. Since most of these proteins participate in the repair of DNA double-strand breaks (DSBs), this was perceived by
many authors as a paradox, given that telomeres function to conceal natural DNA ends from mechanisms that detect and repair
DSBs. However, we argue here that the key function of one particular DSB protein, Ku, is to prevent or control access of telomerase,
the enzyme that synthesises telomeric sequences, to both internal DSBs and natural chromosomal ends. This view is supported
by observations that Ku has a high affinity for DNA ends; it acts as a negative regulator of telomerase and that telomerase
itself can target internal DSBs. Ku then directs other DSB repair/telomere maintenance proteins to either repair DSBs at internal
chromosomal sites or prevent uncontrolled elongation of telomeres by telomerase. This model eliminates the above paradox and
provides a testable scenario in which the role of DSB repair proteins is to protect chromosomal integrity by balancing repair
activities and telomere maintenance. In our model, a close association between telomeres and different DNA damage response
factors is not an unexpected event, but rather a logical result of chromosomal integrity maintenance activities.
Review related to the 15th International Chromosome Conference (ICC XV), held in September 2004, Brunel University, London,
UK 相似文献
43.
A simple, fast and sensitive method was developed to verify the presence of
the sialyl Lewis(x) antigen on an N-linked glycoprotein. High performance
liquid chromatography-electrospray mass spectrometry (HPLC-ESI/MS) was used
to identify which of the five N-linked glycosylation sites of human plasma
alpha1-acid-glycoprotein (orosomucoid, OMD) contain the sialyl Lewis(x)
antigen. OMD was digested with proteolytic enzymes and analyzed by reversed
phase chromatography coupled with on-line ESI/MS. A tandem mass
spectrometry experiment was designed to detect the presence of the sialyl
Lewis(x) antigen based on the observation of an 803 mass to charge ratio (
m/z ) ion produced in the intermediate pressure region of the ESI
interface. The ESI/MS signal at m/z 803 is consistent with an oxonium ion
for a glycan structure containing NeuAc, Gal, GlcNAc, and Fuc. The identity
of the m/z 803 ion was confirmed by ESI/MS/MS analysis of the m/z 803
fragment ion and comparison with a sialyl Lewis(x) standard. The
stereochemistry and linkage positions were assigned using previous NMR
analysis but could be determined with permethylation analysis if necessary.
The analysis of OMD gave a pattern showing signal for the sialyl Lewis(x)
antigen coeluting with each of the five N-linked glycopeptides. The ability
to monitor sialyl Lewis(x) expression at each of the five sites is of
interest in the study of OMD's role in inflammatory diseases.
相似文献
44.
45.
Murine severe combined immunodeficiency (scid) cells are characterized by defective Prkdc (DNA-PKcs), one of the key genes involved in the repair of DNA double-strand breaks. Interestingly, scid mice are not null mutants and their cells are likely to show low DNA-PKcs activity. Prkdc is also involved in telomere maintenance and in contrast to mice genetically engineered to lack Prkdc (i.e. null mutants), which show complete absence of DNA-PKcs activity, loss of telomere capping function and normal telomere length, cells from scid mice show not only loss of telomere capping function but also abnormally elongated telomeres. Here we demonstrate that telomere elongation observed in murine scid cells can be reversed by expressing mutant hRAD54, a protein involved in homologous recombination. In addition, we measured recombination rates at telomeres using chromosome orientation fluorescence in situ hybridization (CO-FISH) and found that these are elevated in scid cells in comparison with control cells, or significantly reduced in scid cells expressing mutant hRAD54. Similarly, recombination rates at telomeres are reduced in scid cells following introduction of functional Prkdc. Since expression of mutant hRAD54 and restoration of functional Prkdc in scid cells cause the same effects, i.e. telomere shortening and reduced recombination rates at telomeres, these results argue that telomere elongation in scid cells is a complex trait resulting from interactions between homologous recombination mechanisms and DNA-PKcs. 相似文献
46.
Survival of vegetation on soil-capped mining wastes is often impaired during dry seasons due to the limited amount of water stored in the shallow soil capping. Growth and survival of Rhodes grass (Chloris gayana) during soil drying on various layered capping sequences constructed of combinations of topsoil, subsoil, seawater-neutralised residue sand and low grade bauxite was determined in a glasshouse. The aim was to describe the survival of Rhodes grass in terms of plant and soil water relationships. The soil water characteristic curve and soil texture analysis was a good predictor of plant survival. The combination of soil with a high water holding capacity and low soil water diffusivity (e.g. subsoil with high clay contents) with soil having a high water holding capacity and high diffusivity (e.g. residue sand) gave best survival during drying down (up to 88 days without water), whereas topsoil and low grade bauxite were unsuitable (plants died within 18–39 days). Clayey soil improved plant survival by triggering a water stress response during peak evaporative water demand once residue sand dried down and its diffusivity fell below a critical range. Thus, for revegetation in seasonally dry climates, soil capping should combine one soil with low diffusivity and one or more soils with high total water holding capacity and high diffusivity. 相似文献
47.
Althaf Hussain Shaik Nayab Rasool Shaik Abdul Kareem Mohammed Suliman Yousef Al Omar Altaf Mohammad Talal Abdulaziz Mohaya Lakshmi Devi Kodidhela 《Saudi Journal of Biological Sciences》2018,25(3):431-436
The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE) on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON) in isoproterenol (ISO)-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C) from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500?mg/kg body weight (bw) and gallic acid (15?mg/kg bw) for 30?days challenged with concurrent injection of ISO (85?mg/kg bw) on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. 相似文献
48.
Esther N. Mwangi Shawgi M. Hassan Godwin P. Kaaya Suliman Essuman 《Experimental & applied acarology》1997,21(2):117-126
In an experiment to investigate the effect of the tick parasitoid, Ixodiphagus hookeri, on tick numbers on cattle, 150 000 parasitoids were released over a period of 1 year in a field where ten cattle infested with multiple tick species were kept. Amblyomma variegatum was reduced from 44 to two ticks per animal while Rhipicephalus appendiculatus increased over the time of parasitoid release. During the time of release 51% of the nymphs of A. variegatum collected from the animals were parasitized. The recovery of the parasitoids after the releases were stopped was only 9%. The total numbers of A. variegatum remained low up to 1 year after the parasitoid release was stopped. This study gives an insight into how I. hookeri could be used strategically for the management of A. variegatum on small-scale farms. 相似文献
49.
Shaik Althaf Hussain Mohammed Abdul Kareem Shaik Nayab Rasool Suliman Yousef Al Omar Alwasel Saleh Manal Abdulrahman Al-Fwuaires Jayasimha Rayalu Daddam Kodidhela Lakshmi Devi 《Biological trace element research》2018,181(1):112-121
The trace elements and minerals in Terminalia pallida fruit ethanolic extract (TpFE) were determined by the instrument inductively coupled plasma-mass spectrometry (ICP-MS), and the cardioprotection of TpFE against isoproterenol (ISO)-administered rats was studied. Rats were pretreated with TpFE (100, 300, and 500 mg/kg bw) for 30 days, with concurrent administration of ISO (85 mg/kg bw) for two consecutive days. The levels of trace elements and minerals in TpFE were below the permitted limits of World Health Organization standards. ISO administration significantly increased the heart weight and cardiac marker enzymes in serum, xanthine oxidase, sodium, and calcium in the heart, whereas significantly decreased body weight, reduced glutathione, glutathione-S-transferase, superoxide dismutase, and potassium in the heart. Oral pretreatment of TpFE significantly prevented the ISO-induced alterations. This is the first report that revealed the determination of trace elements and mineral nutrients of TpFE by ICP-MS which plays a principal role in the herbal drug discovery for the treatment of cardiovascular diseases. 相似文献
50.
MSCs ameliorates DPN induced cellular pathology via [Ca2+]i homeostasis and scavenging the pro‐inflammatory cytokines
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