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71.
Gyula Szabó Gábor L. Kovács Lajos Baláspiri Gyula Telegdy 《Neurochemical research》1986,11(12):1677-1682
The effects of graded doses ofd-pipecolic acid (0.005–5 g/animals s.c.) on tolerance to the hypothermic effect of ethanol (4 g/kg i.p.) were investigated in mice.d-pipecolic acid itself did not change the core temperature or the acute hypothermic response to a single dose of ethanol. Repeatedd-pipecolic acid administration, however, blocked the development of tolerance to the hypothermic effect of ethanol. The development of tolerance could be observed in the control group. It is assumed thatd-pipecolic acid is capable of counteracting the tolerance effect of ethanol. 相似文献
72.
Szabolcs Lengyel Bla Mester Mrton Szabolcs Csaba Szepesvry Gyula Szab Lszl Polyk Zoltn Boros Edvrd Mizsei Kristf Mlns Thomas O. Mr Csaba Aradi 《Restoration Ecology》2020,28(5):1087-1099
Ecosystem restoration implies focusing on multiple trophic levels and ecosystem functioning, yet higher trophic levels, that is, animals, are less frequently targeted by restoration than plants. Habitat diversity, the spatial heterogeneity between and within habitat patches in a landscape, is a well‐known driver of species diversity, and offers possible ways to increase species diversity at multiple trophic levels. We argue that habitat diversity is central in whole‐ecosystem restoration as we review its importance, provide a practical definition for its components, and propose ways to target it in restoration. Restoration targeting habitat diversity is used commonly in aquatic ecosystems, mostly to increase the physical diversity of habitats, meant to provide more niches available to a higher number of animal species. To facilitate the uptake of habitat diversity in terrestrial ecosystem restoration, we distinguish between compositional and structural habitat diversity, because different animal groups will respond to different aspects of habitat diversity. We also propose four methods to increase habitat diversity: varying the starting conditions to obtain divergent successional pathways, emulating natural disturbances, establishing keystone structures, and applying ecosystem engineer species. We provide two case studies to illustrate how these components and methods can be incorporated in restoration. We conclude that targeting habitat diversity is a promising way to restore habitats for a multitude of species of animals and plants, and that it should become mainstream in restoration ecology and practice. We encourage the restoration community to consider compositional and structural habitat diversity and to specifically target habitat diversity in ecosystem restoration. 相似文献
73.
Anna N. Tevyashova Elena N. Bychkova Alexander M. Korolev Elena B. Isakova Elena P. Mirchink Ilya A. Osterman Réka Erdei Zsolt Szücs Gyula Batta 《Bioorganic & medicinal chemistry letters》2019,29(2):276-280
One of the promising directions of the combined approach is the design of dual-acting antibiotics – heterodimeric structures on the basis of antimicrobial agents of different classes. In this study a novel series of azithromycin-glycopeptide conjugates were designed and synthesized. The structures of the obtained compounds were confirmed using NMR spectroscopy and mass spectrometry data including MS/MS analysis. All novel hybrid antibiotics were found to be either as active as azithromycin and vancomycin against Gram-positive bacterial strains or have superior activity in comparison with their parent antibiotics. One compound, eremomycin-azithromycin conjugate 16, demonstrated moderate activity against Enterococcus faecium and Enterococcus faecalis strains resistant to vancomycin, and equal to vancomycin’s activity for the treatment of mice with Staphylococcus aureus sepsis. 相似文献
74.
Acsadi G Moore SA Chéron A Delalande O Bennett L Kupsky W El-Baba M Le Rumeur E Hubert JF 《The Journal of biological chemistry》2012,287(22):18153-18162
Mutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T>C) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin. 相似文献
75.
Minorics R Bózsity N Wölfling J Mernyák E Schneider G Márki A Falkay G Ocsovszki I Zupkó I 《The Journal of steroid biochemistry and molecular biology》2012,132(1-2):168-175
The possibility of the therapeutic use of estrogens emerged following the recognition that certain estradiol analogs, and particularly metabolites (e.g. the A-ring metabolite 2-hydroxyestrone, etc.) inhibit the differentiation of diverse tumor cell lines. Until recently, despite the investigation of numerous synthetic d-ring-substituted estrone derivatives, no analysis had been published on the effects of D-ring expansion of estrone on its tumor-suppressing activity. The aim of the present study was to characterize the antiproliferative effects of normal and 13-epi-D-homoestrone and their 3-methyl ethers (1-4) on human reproductive cancer cell lines. The antitumor activities of the two epimer pairs on HeLa, MCF-7 and Ishikawa cells were determined. Normal D-homoestrone exerted the greatest cytostatic effect on HeLa cells (IC(50)=5.5 μM) and was subjected to further investigations to elucidate its mechanism of action on apoptosis induction. Morphological changes detected by Hoechst 33258-propidium iodide double staining, the cell cycle arrest at phase G2/M and the subsequent increase in the proportion of the subG1 fraction determined by flow cytometric analysis and the significant increase in the activity of caspase-3 confirmed the induction of apoptosis in HeLa cells treated with D-homoestrone. D-Homoestrone was also tested on a non-cancerous human lung fibroblast cell line (MRC-5) to determine its selective toxicity. The concentration in which it inhibited cell proliferation by 50% was at least six times higher for the fibroblast cells than for cervical cancer cells. No significant in vivo estrogenic activity was observed as concerns the uterus weight of gonadectomized rats after a 7-day treatment with normal D-homoestrone. These results led to the conclusion that normal D-homoestrone is a novel antitumor compound with a similar activity on HeLa cells as that of the reference agent cisplatin, but its selectivity toward non-cancerous cells is significantly higher than that of cisplatin. It may be considered to be a basic lead molecule for the preclinical development of potential anticancer agents. 相似文献
76.
1,4-Anhydro-D-fructose and 1,4-anhydro-D-tagatose were prepared from 1,2-O-isopropylidene-D-glucofuranose via the common intermediate 3,5,6-tri-O-benzyl-D-glucitol. The title compounds may be interesting anti-oxidants and feature activities akin to their natural pyranoid counterpart, 1,5-anhydro-D-fructose. 相似文献
77.
The endomorphins (EM1 and EM2) are selective endogenous ligands for mu-opioid receptors (MOR1 and MOR2) with neurotransmitter
and neuromodulator roles in mammals. In the present study we investigated the potential actions of EMs on striatal GABA release
and the implication of different MORs in these processes. Rat striatal slices were preincubated with tritium-labelled GABA
([3H]GABA), pretreated with selective MOR1 and MOR2 antagonist beta-funaltrexamine and selective MOR1 antagonist naloxonazine
and then superfused with the selective MOR agonists, EM1 and EM2. EM1 significantly decreased the striatal [3H]GABA release induced by electrical stimulation. Beta-funaltrexamine antagonized the inhibitory action of EM1, but naloxonazine
did not affect it considerably. EM2 was ineffective, even in case of specific enzyme inhibitor diprotin A pretreatment. The
results demonstrate that EM1 decreases GABA release in the basal ganglia through MOR2, while EM2 does not influence it. 相似文献
78.
Kathryn J. Swoboda Charles B. Scott Sandra P. Reyna Thomas W. Prior Bernard LaSalle Susan L. Sorenson Janine Wood Gyula Acsadi Thomas O. Crawford John T. Kissel Kristin J. Krosschell Guy D'Anjou Mark B. Bromberg Mary K. Schroth Gary M. Chan Bakri Elsheikh Louise R. Simard 《PloS one》2009,4(5)
Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2–3 years, 29 SMA type II ages 2–14 years and 11 type III ages 2–31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p≤0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Δ7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p≤0.0036) and maximum ulnar CMAP scores (p≤0.0001) increased significantly.
Conclusions
While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects.Trial Registration
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00374075?term=NCT00374075&rank=1 相似文献79.
Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours
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Maria V. Yusenko Dmitry Zubakov Gyula Kovacs 《International journal of biological sciences》2009,5(6):517-527
Due to overlapping morphology, malignant chromophobe renal cell carcinomas (RCC) and benign renal oncocytomas (RO) may pose a diagnostic problem. In the present study, we have applied different algorithms to evaluate the data sets obtained by hybridisation of pooled and also individual samples of renal cell tumours (RCT) onto two different gene expression platforms. The two approaches revealed high similarities in the gene expression profiles of chromophobe RCCs and ROs but also some differences. After identifying the differentially expressed genes by statistic analyses, the candidate genes were further selected by a real time and normal RT-PCR and their products were analysed by immunohistochemistry. We have identified CD82 and S100A1 as valuable markers for chromophobe RCC as well as AQP6 for ROs. However, these genes are expressed at the protein level in other types of RCTs as well albeit at a low frequency and low intensity. As none of the selected genes marks exclusively one type of RCTs, for the differential diagnosis of chromophobe RCCs and ROs, a set of markers such as CD82, S100A1 and AQP6 as well as some others would be an option in routine histological laboratories. 相似文献
80.
Gyula Diszhzi Zsuzsanna . Magyar Erika Lisztes Edit Tth-Molnr Pter P. Nnsi Rudi Vennekens Balzs I. Tth Jnos Almssy 《The Journal of biological chemistry》2021,297(3)
Transient receptor potential cation channel subfamily M member 4 (TRPM4) is a Ca2+-activated nonselective cation channel that mediates membrane depolarization. Although, a current with the hallmarks of a TRPM4-mediated current has been previously reported in pancreatic acinar cells (PACs), the role of TRPM4 in the regulation of acinar cell function has not yet been explored. In the present study, we identify this TRPM4 current and describe its role in context of Ca2+ signaling of PACs using pharmacological tools and TRPM4-deficient mice. We found a significant Ca2+-activated cation current in PACs that was sensitive to the TRPM4 inhibitors 9-phenanthrol and 4-chloro-2-[[2-(2-chlorophenoxy)acetyl]amino]benzoic acid (CBA). We demonstrated that the CBA-sensitive current was responsible for a Ca2+-dependent depolarization of PACs from a resting membrane potential of −44.4 ± 2.9 to −27.7 ± 3 mV. Furthermore, we showed that Ca2+ influx was higher in the TRPM4 KO- and CBA-treated PACs than in control cells. As hormone-induced repetitive Ca2+ transients partially rely on Ca2+ influx in PACs, the role of TRPM4 was also assessed on Ca2+ oscillations elicited by physiologically relevant concentrations of the cholecystokinin analog cerulein. These data show that the amplitude of Ca2+ signals was significantly higher in TRPM4 KO than in control PACs. Our results suggest that PACs are depolarized by TRPM4 currents to an extent that results in a significant reduction of the inward driving force for Ca2+. In conclusion, TRPM4 links intracellular Ca2+ signaling to membrane potential as a negative feedback regulator of Ca2+ entry in PACs. 相似文献