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121.
122.
Zoltán Nemes Krisztina Takács-Novák Gergely Völgyi Klara Valko Szabolcs Béni Zoltán Horváth Bálint Szokol Nóra Breza Judit Dobos Csaba Szántai-Kis Eszter Illyés Sándor Boros Robbert Jan Kok László Őrfi 《Bioorganic & medicinal chemistry letters》2018,28(14):2391-2398
Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration. 相似文献
123.
Zsolt Szeleczky Sándor Semsey Péter Bagi Emese Pálovics Ferenc Faigl Elemér Fogassy 《Chirality》2016,28(3):230-234
In order to develop a resolution procedure for a given racemic compound, the first and the most important step is finding the most suitable resolving agent. We studied 18 individual resolutions that were carried out with resolving agents having high eutectic composition. We found that very high enantiomeric excess values were obtained in all cases. We assume that the eutectic composition of a given resolving agent is one of the most important properties that should always be considered during the search for the most efficient resolving agent. Chirality 28:230–234, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
124.
In eastern Central Europe the abandonment of traditional land use represents a major threat for biodiversity. Evidence on species loss and shifts in assemblages is often based on butterfly surveys since these are known as sensitive indicators of habitat changes. Butterfly assemblages were studied in meadows of the Transcarpathian lowland in three consecutive years (2012–2014) with standard transect walks in six different sites (two transects/site). More than 6500 individuals of 66 species were recorded. The less disturbed habitats surrounded by natural forests have shown the highest diversity (Shannon-Wiener, dominance profiles). In faunal types the widely distributed, generalist Euro-Siberian species predominated with significant presence of Holo-Mediterranean and southern Continental elements. Three main types of habitats were separated and characterised by indicator species, i.e. we hierarchically classified the species according to their fidelity by the IndVal method. The dry sites were characterised by a few generalist species only, while the humid ones and mostly the transitional sites were inhabited by numerous habitat and/or food plant specialists. The assemblages were compared with multivariate analysis and the concordance of inter-annual changes of the assemblages were surveyed. The concordance profiles of the less diverse dry habitats were clearly separated from others while other sites with dominance profiles with longer sequence of scarce species have also shown similar concordance profiles. The importance of nature-like forest fringe structures was pointed out for both habitat and species conservation. Conservation efforts should be focused to sustain the general level of biodiversity by the preservation of nature-like habitats and the possible re-establishment of some kinds of traditional use. 相似文献
125.
Tomasz W. Pyrcz Haydon Warren-Gash Jadwiga Lorenc-Brudecka Dieuwko?Knoop Philippe Oremans Szabolcs Sáfián 《ZooKeys》2013,(298):1-37
Updated data on the distribution, ecology and taxonomy of Euphaedra cyparissa (Cramer) and Euphaedra sarcoptera (Butler) are presented. Three new subspecies of Euphaedra cyparissa and one of Euphaedra sarcoptera are described and their geographic distribution is presented. The monophyly of the genus Euphaedra sensu Hecq is assessed based on morphological, in particular male and female genitalia, and behavioural traits. Possible evolutionary reasons for the convergence of colour pattern between the sympatric subspecies of Euphaedra cyparissa and Euphaedra sarcoptera are discussed. 相似文献
126.
127.
A key event in development is the irreversible commitment to a particular cell fate, which may be concurrent with or delayed with respect to the initial cell fate decision. In this work, we use the paradigmatic bacteriophage λ lysis-lysogeny decision circuit to study the timing of commitment. The lysis-lysogeny decision is made based on the expression trajectory of CII. The chosen developmental strategy is manifested by repression of the pR and pL promoters by CI (lysogeny) or by antitermination of late gene expression by Q (lysis). We found that expression of Q in trans from a plasmid at the time of infection resulted in a uniform lytic decision. Furthermore, expression of Q up to 50 min after infection results in lysis of the majority of cells which initially chose lysogenic development. In contrast, expression of Q in cells containing a single chromosomal prophage had no effect on cell growth, indicating commitment to lysogeny. Notably, if the prophage was present in 10 plasmid-borne copies, Q expression resulted in lytic development, suggesting that the cellular phage chromosome number is the critical determinant of the timing of lysogenic commitment. Based on our results, we conclude that (i) the lysogenic decision made by the CI-Cro switch soon after infection can be overruled by ectopic Q expression at least for a time equivalent to one phage life cycle, (ii) the presence of multiple λ chromosomes is a prerequisite for a successful Q-mediated switch from lysogenic to lytic development, and (iii) phage chromosomes within the same cell can reach different decisions. 相似文献
128.
Sipeki S Bander E Parker PJ Faragó A 《Biochemical and biophysical research communications》2006,339(1):122-125
The modulation of phosphoinositide 3-kinase (PI3K) activity influences the quality of cellular responses triggered by various receptor tyrosine kinases. Protein kinase C (PKC) has been reported to phosphorylate signalling molecules upstream of PI3K and thereby it may affect the activation of PI3K. Here, we provide the first evidence for a direct effect of a PKC isoenzyme on the activity of PI3K. PKCalpha but not PKCepsilon phosphorylated the catalytic subunit of the p110alpha/p85alpha PI3K in vitro in a manner inhibited by the PKC inhibitor bisindolylmaleimide I (BIM I). The incubation of PI3K with active PKCalpha resulted in a significant decrease in its lipid kinase activity and this effect was also attenuated by BIM I. We conclude that PKCalpha is able to modulate negatively the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunit. 相似文献
129.
Hungarian sodic water bodies have a rich macro- and microcrustacean fauna due to the lack of fish populations. The crustacean
population is very abundant, for this reason these wetlands provide good feeding resources for waterbirds. The density of
macro- and microcrustacean populations together with feeding waterbirds was investigated in March, April, and May of 2002,
on two characteristic sodic pans, “Kelemen-szék” and “Zab-szék”. The following dabbling-filtering waterfowls and pelagic forager
wader species were counted: northern pintail (Anas acuta), northern shoveler (Anas clypeata), garganey (Anas querquedula), common teal (Anas crecca), avocet (Recurvirostra avosetta), spotted redshank (Tringa erythropus), greenshank (Tringa nebularia), and marsh sandpiper (Tringa stagnatilis). The dominant macrocrustacean species was the [Anostraca – Branchinectidae] natronophile Branchinecta orientalis, and its density was significantly higher in Zab-szék than in Kelemen-szék. The microcrustacean zooplankton community was
also different in the pans, [Cladocera] Daphnia magna density was significantly higher in Kelemen-szék than in Zab-szék, but the density of the [Copepoda] natronophile Arctodiaptomus spinosus, was higher in Zab-szék than in Kelemen-szék. The density of the investigated waterbird species was also significantly higher
in Zab-szék than in Kelemen-szék during spring. We can conclude that the macrocrustacean B. orientalis is one of the most important potential food resources for migrating pelagic foraging waders in spring on characteristic Hungarian
sodic pans. However, the most abundant available food item for waterbirds are copepod microcrustacean zooplankton, which have
a biomass that is larger by approximately one order of magnitude than the macrocrustacean zooplankton biomass. Considering
the lack of submerged water vegetation, we suggest that planktonic microcrustaceans are an important food resource for dabbling-filtering
ducks because they can utilise the small crustacean biomass more effectively than the less abundant and rapidly moving macrocrustacean
B. orientalis. 相似文献
130.
Adrienn Borsy János Podani Viktor Stéger Bernadett Balla Arnold Horváth János P. Kósa István Gyurján Jr Andrea Molnár Zoltán Szabolcsi László Szabó Eéna Jakó Zoltán Zomborszky János Nagy Szabolcs Semsey Tibor Vellai Péter Lakatos László Orosz 《Molecular genetics and genomics : MGG》2009,281(3):301-313
Osteoporosis attacks 10% of the population worldwide. Humans or even the model animals of the disease cannot recover from
porous bone. Regeneration in skeletal elements is the unique feature of our newly investigated osteoporosis model, the red
deer (Cervus elaphus) stag. Cyclic physiological osteoporosis is a consequence of the annual antler cycle. This phenomenon raises the possibility
to identify genes involved in the regulation of bone mineral density on the basis of comparative genomics between deer and
human. We compare gene expression activity of osteoporotic and regenerating rib bone samples versus autumn dwell control in
red deer by microarray hybridization. Identified genes were tested on human femoral bone tissue from non-osteoporotic controls
and patients affected with age-related osteoporosis. Expression data were evaluated by Principal Components Analysis and Canonical
Variates Analysis. Separation of patients into a normal and an affected group based on ten formerly known osteoporosis reference
genes was significantly improved by expanding the data with newly identified genes. These genes include IGSF4, FABP3, FABP4, FKBP2, TIMP2, TMSB4X, TRIB, and members of the Wnt signaling. This study supports that extensive comparative genomic analyses, here deer and human, provide
a novel approach to identify new targets for human diagnostics and therapy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献