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81.
Aims
The diverse physiological functions of histamine are mediated through distinct histamine receptors. In this study we investigated the role of H2R and H4R in the effects of histamine on the production of reactive oxygen species by phagocytes in whole blood.Main methods
Changes in reactive oxygen species (ROS) production by whole blood phagocytes after treatment with histamine, H4R agonists (4-methylhistamine, VUF8430), H2R agonist (dimaprit) and their combinations with H4R antagonist (JNJ10191584) and H2R antagonist (ranitidine) were determined using the chemiluminescence (CL) assay. To exclude the direct scavenging effects of the studied compounds on the CL response, the antioxidant properties of all compounds were measured using several methods (TRAP, ORAC, and luminol–HRP–H2O2 based CL).Key findings
Histamine, 4-methylhistamine, VUF8430 and dimaprit inhibited the spontaneous and OZP-activated whole blood CL in a dose-dependent manner. On the other hand, only VUF8430 was able to inhibit PMA-activated whole blood CL. Ranitidine, but not JNJ10191584, completely reduced the effects of histamine, 4-methylhistamine and dimaprit. The direct scavenging ability of tested compounds was negligible.Significance
Our results demonstrate that the inhibitory effects of histamine on ROS production in whole blood phagocytes were caused by H2R. Our results also suggest that H4R agonists in concentrations higher than 10− 6 M may also influence ROS production via binding to H2R. 相似文献82.
Nathalie Vrielynck Katja Schneider Marion Rodriguez Jason Sims Aurlie Chambon Aurlie Hurel Arnaud De
Muyt Arnaud Ronceret Ondrej Krsicka Christine Mzard Peter Schlgelhofer Mathilde Grelon 《Nucleic acids research》2021,49(17):9821
In the current meiotic recombination initiation model, the SPO11 catalytic subunits associate with MTOPVIB to form a Topoisomerase VI-like complex that generates DNA double strand breaks (DSBs). Four additional proteins, PRD1/AtMEI1, PRD2/AtMEI4, PRD3/AtMER2 and the plant specific DFO are required for meiotic DSB formation. Here we show that (i) MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, (ii) PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between the DSB-forming and resection machineries, (iii) DFO controls MTOPVIB foci formation and is part of a divergent RMM-like complex including PHS1/AtREC114 and PRD2/AtMEI4 but not PRD3/AtMER2, (iv) PHS1/AtREC114 is absolutely unnecessary for DSB formation despite having a conserved position within the DSB protein network and (v) MTOPVIB and PRD2/AtMEI4 interact directly with chromosome axis proteins to anchor the meiotic DSB machinery to the axis. 相似文献
83.
Lukáš Opálka Jason M. Meyer Veronika Ondrejčeková Linda Svatošová Franz P.W. Radner Kateřina Vávrová 《Journal of lipid research》2022,63(6):100226
Epidermal omega-O-acylceramides (ω-O-acylCers) are essential components of a competent skin barrier. These unusual sphingolipids with ultralong N-acyl chains contain linoleic acid esterified to the terminal hydroxyl of the N-acyl, the formation of which requires the transacylase activity of patatin-like phospholipase domain containing 1 (PNPLA1). In ichthyosis with dysfunctional PNPLA1, ω-O-acylCer levels are significantly decreased, and ω-hydroxylated Cers (ω-OHCers) accumulate. Here, we explore the role of the linoleate moiety in ω-O-acylCers in the assembly of the skin lipid barrier. Ultrastructural studies of skin samples from neonatal Pnpla1+/+ and Pnpla1-/- mice showed that the linoleate moiety in ω-O-acylCers is essential for lamellar pairing in lamellar bodies, as well as for stratum corneum lipid assembly into the long periodicity lamellar phase. To further study the molecular details of ω-O-acylCer deficiency on skin barrier lipid assembly, we built in vitro lipid models composed of major stratum corneum lipid subclasses containing either ω-O-acylCer (healthy skin model), ω-OHCer (Pnpla1-/- model), or combination of the two. X-ray diffraction, infrared spectroscopy, and permeability studies indicated that ω-OHCers could not substitute for ω-O-acylCers, although in favorable conditions, they form a medium lamellar phase with a 10.8 nm-repeat distance and permeability barrier properties similar to long periodicity lamellar phase. In the absence of ω-O-acylCers, skin lipids were prone to separation into two phases with diminished barrier properties. The models combining ω-OHCers with ω-O-acylCers indicated that accumulation of ω-OHCers does not prevent ω-O-acylCer-driven lamellar stacking. These data suggest that ω-O-acylCer supplementation may be a viable therapeutic option in patients with PNPLA1 deficiency. 相似文献
84.
Nucleotide pyrophosphotransferase (NPT) activity of two Streptomyces griseus strains was studied in submerged culture during their life cycle. NPT activity could be detected only in the culture filtrate but not in the membrane fraction or in cell extract of the sporulating (streptomycin-non-producing) S. griseus No. 45-H. No enzyme could be detected in the non-sporulating (streptomycin-producing) S. griseus No 52--1 cultures. 相似文献
85.
Kamil Musilek Ondrej Holas Kamil Kuca Daniel Jun Vlastimil Dohnal Martin Dolezal 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):425-432
Nine potential non-symmetrical xylene-bridged AChE reactivators were synthesized using modifications of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and the insecticide paraoxon together with nine symmetrical xylene-bridged compounds, was tested in vitro. Seven compounds were promising against paraoxon-inhibited AChE. Two compounds were found to be more potent against tabun-inhibited AChE than obidoxime at a concentration applicable in vivo. 相似文献
86.
Eva Mezeiova Katarina Spilovska Eugenie Nepovimova Lukas Gorecki Ondrej Soukup Rafael Dolezal 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):583-606
Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease. 相似文献
87.
Ondrej Benek Lukas Hroch Laura Aitken Frank Gunn-Moore Lucie Vinklarova Kamil Kuca 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):665-670
Several neurodegenerative disorders including Alzheimer’s disease (AD) have been connected with deregulation of casein kinase 1 (CK1) activity. Inhibition of CK1 therefore presents a potential therapeutic strategy against such pathologies. Recently, novel class of CK1-specific inhibitors with N-(benzo[d]thiazol-2-yl)-2-phenylacetamide structural scaffold has been discovered. 1-(benzo[d]thiazol-2-yl)-3-phenylureas, on the other hand, are known inhibitors amyloid-beta binding alcohol dehydrogenase (ABAD), an enzyme also involved in pathophysiology of AD. Based on their tight structural similarity, we decided to evaluate series of previously published benzothiazolylphenylureas, originally designed as ABAD inhibitors, for their inhibitory activity towards CK1. Several compounds were found to be submicromolar CK1 inhibitors. Moreover, two compounds were found to inhibit both, ABAD and CK1. Such dual-activity could be of advantage for AD treatment, as it would simultaneously target two distinct pathological processes involved in disease’s progression. Based on PAMPA testing both compounds were suggested to permeate the blood-brain barrier, which makes them, together with their unique dual activity, interesting lead compounds for further development. 相似文献
88.
Genome‐wide identification of urinary cell‐free microRNAs for non‐invasive detection of bladder cancer 下载免费PDF全文
Jaroslav Juracek Barbora Peltanova Jan Dolezel Michal Fedorko Dalibor Pacik Lenka Radova Petra Vesela Marek Svoboda Ondrej Slaby Michal Stanik 《Journal of cellular and molecular medicine》2018,22(3):2033-2038
Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non‐invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT‐PCR. Whole‐genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR‐31‐5p, miR‐93‐5p and miR‐191‐5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2‐miRNA‐based urinary DxScore (miR‐93‐5p, miR‐31‐5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post‐operatively. In conclusion, we identified and independently validated cell‐free urinary miRNAs as promising biomarkers enabling non‐invasive detection of BCA. 相似文献
89.
Evolutionary history as a driver of ecological networks: a case study of plant–hummingbird interactions 下载免费PDF全文
Multiple factors drive species interactions in ecological networks, such as morphological barriers, spatio–temporal distribution, abundances and evolutionary histories of species. Novel methods are making it possible to evaluate the relative importance of each of these drivers. However, the lack of appropriate methods has prevented evaluating the extent to which interaction networks are shaped by species’ evolutionary histories. This study includes the evolutionary histories of species among the potential drivers of interactions, allowing the comparative analysis of its importance in structuring ecological networks. We hypothesized different possible phylogenetic scenarios to predict frequencies of interactions between species by combining concepts from the fields of ecological networks and ecophylogenetics. The usage of these scenarios is illustrated in a plant–hummingbird interaction network database from the Atlantic Forest, southeastern Brazil. We first evaluated which phylogenetic hypotheses better predict the observed network; subsequently, we evaluated the relative importance of species evolutionary histories, abundances, and matching on species morphologies and phenologies as drivers of their frequencies of interactions. The results suggest that the evolutionary histories of hummingbirds are more important than the species abundances in structuring the studied plant–hummingbird network but less important than the morphological and phenological matching among species. The approach developed here offers the potential to advance our understanding of the multiple factors structuring ecological networks. 相似文献
90.
Trophic niche,capture efficiency and venom profiles of six sympatric ant‐eating spider species (Araneae: Zodariidae) 下载免费PDF全文
Stano Pekár Lenka Petráková Ondrej Šedo Stanislav Korenko Zbyněk Zdráhal 《Molecular ecology》2018,27(4):1053-1064
The arms race between specialist predators and their prey has resulted in the evolution of a variety of specific adaptations. In venomous predators, this can include venom composition, particularly if predators are specialized on dangerous prey. Here, we performed an integrative study using six species of highly specialized ant‐eating spiders of the genus Zodarion to investigate their phylogeny, realized trophic niche, efficacy in the capture of various ant species and venom composition. Data on natural diet obtained by next‐generation sequencing and field observations showed that the six Zodarion species exploit different ant species. Their phylogeny, based on mitochondrial and nuclear genes, correlated with the composition of their natural prey, indicating that closely related Zodarion species specialize on similar ant species. Prey‐capture parameters differed among Zodarion species suggesting prey‐specific efficacy. Similarly, the venom profiles of both low and high molecular compounds differed among species. Only the profiles of low molecular compounds were correlated with capture efficacy parameters, suggesting that the venom of Zodarion spiders contains prey‐specific components. Our study suggests that Iberian Zodarion spiders are specialized on particular ant species. 相似文献