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231.
Géraldine Piessevaux Virginie Lella Michèle Rivière Daniel Stieber Pierre Drèze Josiane Szpirer Claude Szpirer 《Mammalian genome》2009,20(1):43-52
We previously defined quantitative trait loci (QTLs) that control susceptibility to 7,12-dimethylbenz(α)anthracene-induced
mammary carcinoma in SPRD-Cu3 (susceptible) and WKY (resistant) rats. Two of these QTLs, assigned to chromosomes (Chr) 10
and 18, control tumor growth rate and invasiveness. In this study we characterized a congenic strain in which a large segment
of WKY Chr 10 was introduced in the SPRD-Cu3 genetic background and demonstrated that this chromosome segment controls this
tumor trait. The WKY allele at this QTL (Mcsta1) reduces the growth rate of the fastest growing tumors by 26%. We also previously showed that two SPRD-Cu3-WKY congenic strains
containing a WKY chromosome segment derived either from Chr 5 or from Chr 18 exhibit a reduction in tumor multiplicity (QTLs
Msctm1 and Mcstm2, respectively) (with no reduction in tumor growth rate in the Chr 18 congenic). In this study we generated a double congenic
strain, which contains the two WKY differential segments from Chr 5 and 18, to determine how these two segments interact with
one another. Interestingly, two types of epistatic interactions were found: no additive effect was seen with respect to tumor
multiplicity, while a reduction in tumor growth rate was observed. It thus appears that WKY alleles located on Chr 5 and Chr
8 interact epistatically in a contrasting manner to modulate tumor multiplicity (in a nonadditive manner) and growth rate
(in a synergic manner). Tumor growth rate is thus influenced by two QTLs, on Chr 10 (Mcsta1) and on Chr 18 (Mcsta2), the action of the latter being dependent on the presence of the Chr5 QTL (Mcstm1). The expression level of positional and functional candidate genes was also analyzed. On Chr 5, Pla2g2a is subject to a syntenic control while expression of the Tp53 (Chr 10) and Pmai1/Noxa (Chr 18) genes appears to be controlled by several mammary cancer resistance QTLs. 相似文献
232.
Pedro Simões Marta Pascual Josiane Santos Michael R Rose Margarida Matos 《BMC evolutionary biology》2009,9(1):133-3
Here we present a correction to our article "Evolutionary dynamics of molecular markers during local adaptation: a case study
in Drosophila subobscura ". We have recently detected an error concerning the application of the Ln RH formula – a test to detect positive selection
– to our microsatellite data. Here we provide the corrected data and discuss its implications for our overall findings. The
corrections presented here have produced some changes relative to our previous results, namely in a locus (dsub14) that presents indications of being affected by positive selection. In general, our populations present less consistent indications
of positive selection for this particular locus in both periods studied – between generations 3 and 14 and between generation
14 and 40 of laboratory adaptation. Despite this, the main findings of our study regarding the possibility of positive selection
acting on that particular microsatellite still hold. As previously concluded in our article, further studies should be performed
on this specific microsatellite locus (and neighboring areas) to elucidate in greater detail the evolutionary forces acting
on this specific region of the O chromosome of Drosophila subobscura. 相似文献
233.
The type I IFNR (interferon receptor) is a heterodimer composed of two transmembrane chains, IFNAR1 (interferon-alpha receptor 1 subunit) and IFNAR2, which are associated with the tyrosine kinases Tyk2 and Jak1 (Janus kinase 1) respectively. Ligand-induced down-regulation of the type I IFNR is a major mechanism of negative regulation of cellular signalling and involves the internalization and lysosomal degradation of IFNAR1. IFNalpha promotes the phosphorylation of IFNAR1 on Ser535, followed by recruitment of the E3 ubiquitin ligase, beta-TrCP2 (beta-transducin repeats-containing protein 2), ubiquitination of IFNAR1 and proteolysis. The non-catalytic role of Tyk2 in sustaining the steady-state IFNAR1 level at the plasma membrane is well documented; however, little is known about the function of Tyk2 in the steps that precede and succeed serine phosphorylation and ubiquitination of IFNAR1 in response to ligand binding. In the present study, we show that catalytic activation of Tyk2 is not essential for IFNAR1 internalization, but is required for ligand-induced IFNAR1 serine phosphorylation, ubiquitination and efficient lysosomal proteolysis. 相似文献
234.
Yélamos J Monreal Y Saenz L Aguado E Schreiber V Mota R Fuente T Minguela A Parrilla P de Murcia G Almarza E Aparicio P Ménissier-de Murcia J 《The EMBO journal》2006,25(18):4350-4360
Poly-(ADP-ribose) polymerase-2 (PARP-2) belongs to a large family of enzymes that synthesize and transfer ADP-ribose polymers to acceptor proteins, modifying their functional properties. PARP-2-deficient (Parp-2-/-) cells, similar to Parp-1-/- cells, are sensitive to both ionizing radiation and alkylating agents. Here we show that inactivation of mouse Parp-2, but not Parp-1, produced a two-fold reduction in CD4+CD8+ double-positive (DP) thymocytes associated with decreased DP cell survival. Microarray analyses revealed increased expression of the proapoptotic Bcl-2 family member Noxa in Parp-2-/- DP thymocytes compared to littermate controls. In addition, DP thymocytes from Parp-2-/- have a reduced expression of T-cell receptor (TCR)alpha and a skewed repertoire of TCRalpha toward the 5' Jalpha segments. Our results show that in the absence of PARP-2, the survival of DP thymocytes undergoing TCRalpha recombination is compromised despite normal amounts of Bcl-xL. These data suggest a novel role for PARP-2 as an important mediator of T-cell survival during thymopoiesis by preventing the activation of DNA damage-dependent apoptotic response during the multiple rounds of TCRalpha rearrangements preceding a positively selected TCR. 相似文献
235.
Stéphanie Godet Céline Loiseau Gaëlle Pencreac’h Françoise Ergan Josiane Hérault 《Journal of phycology》2010,46(4):679-684
Microalgae constitute an interesting novel study area for characterizing new esterases, and so we decided to isolate a complete cDNA encoding a new putative microalgal esterase from the haptophyte Isochrysis galbana Parke. Rapid amplifications of both the 5′ and 3′ cDNA ends (RACE) were performed with specific primers, designed using an incomplete candidate gene from the I. galbana expressed sequence tag (EST) database. The full‐length cDNA obtained was designated IgEst1. The coding sequence was 828 bp long, and the deduced amino acid sequence revealed a polypeptide of 275 amino acids with a predicted signal peptide of 23 residues in the N‐terminal region. The following 252 amino acids formed, after in silico analysis, a mature protein with a molecular mass of ~26.92 kDa and had a theoretical pI of 5.87. Alignment analyses revealed slight but significant identity and similarity with carboxylesterases, phospholipases, and lysophospholipases from various organisms including fungi, plants, and animals. The new sequence IgEst1 enclosed the catalytic triad Ser/Asp/His and the consensus pentapeptide Gly‐X‐Ser‐X‐Gly, two highly conserved patterns found in serine hydrolases. Phylogenetic analyses established a close relationship with putative esterases identified in microalgae genomes. 相似文献
236.
Paulo Filipe Josiane Haigle Jo?o Freitas Afonso Fernandes Jean-Claude Mazière Cécile Mazière René Santus Patrice Morlière 《European journal of biochemistry》2002,269(22):5474-5483
We reported earlier that urate may behave as a pro-oxidant in Cu2+-induced oxidation of diluted plasma. Thus, its effect on Cu2+-induced oxidation of isolated low-density lipoprotein (LDL) was investigated by monitoring the formation of malondialdehyde and conjugated dienes and the consumption of urate and carotenoids. We show that urate is antioxidant at high concentration but pro-oxidant at low concentration. Depending on Cu2+ concentration, the switch between the pro- and antioxidant behavior of urate occurs at different urate concentrations. At high Cu2+ concentration, in the presence of urate, superoxide dismutase and ferricytochrome c protect LDL from oxidation but no protection is observed at low Cu2+ concentration. The use of Cu2+ or Cu+ chelators demonstrates that both copper redox states are required. We suggest that two mechanisms occur depending on the Cu2+ concentration. Urate may reduce Cu2+ to Cu+, which in turn contributes to formation. The Cu2+ reduction is likely to produce the urate radical (UH.-). It is proposed that at high Cu2+ concentration, the reaction of UH.- radical with generates products or intermediates, which trigger LDL oxidation. At low Cu2+ concentration, we suggest that the Cu+ ions formed reduce lipid hydroperoxides to alkoxyl radicals, thereby facilitating the peroxidizing chain reaction. It is anticipated that these two mechanisms are the consequence of complex LDL-urate-Cu2+ interactions. It is also shown that urate is pro-oxidant towards slightly preoxidized LDL, whatever its concentration. We reiterate the conclusion that the use of antioxidants may be a two-edged sword. 相似文献
237.
Chittezhath M Frump AL Jourquin J Lobdell N Eid JE 《Experimental cell research》2008,314(19):3551-3562
The SYT proto-oncoprotein (also known as SS18) is a gene expression regulator conserved across species. Although its biological function is still unknown, the importance of SYT as a housekeeping protein is illustrated by the lethal phenotype of SYT-null embryos. Notably, SYT is a component of the synovial sarcoma-associated translocation product, the SYT-SSX oncogene. SYT was previously reported as a mediator of cell adhesion. In the present study we show that SYT possesses distinct domains that control MDCK cyst formation in three-dimensional collagen cultures. While the carboxy-half of SYT, the QPGY domain, is required for cyst growth, the amino-terminal region appears to exert on this process a regulatory effect. Further analysis suggested that the purinergic G protein-coupled P2Y receptor signaling is involved in SYT-induced cystogenesis. Activation of this cascade is due to facilitation of ATP release in the extracellular space of polarized MDCK cells by SYT. These studies allow us to begin to understand the vital role of SYT in controlling epithelial morphogenesis and might explain the lethality of its loss in the developing embryo. 相似文献
238.
Müller P Chouaïbou M Pignatelli P Etang J Walker ED Donnelly MJ Simard F Ranson H 《Molecular ecology》2008,17(4):1145-1155
Spraying of agricultural crops with insecticides can select for resistance in nontarget insects and this may compromise the use of insecticides for the control of vector-borne diseases. The tolerance of the malaria vector, Anopheles arabiensis to deltamethrin was determined in a field population from a cotton-growing region of Northern Cameroon both prior to and midway through the 4-month period of insecticide application to the cotton crop. A 1.6-fold increase in the median knockdown time was observed. To determine whether this increased tolerance was associated with constitutively elevated levels of genes commonly associated with insecticide resistance, RNA was extracted from F1 progeny from family lines of field-caught mosquitoes and hybridized to the Anopheles gambiae detox chip. The experimental design avoided the confounding effects of colonization, and this study is the first to measure gene expression in the progeny of gravid, wild-caught mosquitoes. Several genes with antioxidant roles, including superoxide dismutases, a glutathione S-transferase and a thioredoxin-dependent peroxidase, and a cytochrome P450 showed elevated expression in mosquito families collected during the insecticide-spraying programme. These genes may constitute an important general defence mechanism against insecticides. Intriguingly, the levels of expression of these genes were strongly correlated suggesting a common regulatory mechanism. 相似文献
239.
Zanatta N Amaral SS Dos Santos JM de Mello DL Fernandes Lda S Bonacorso HG Martins MA Andricopulo AD Borchhardt DM 《Bioorganic & medicinal chemistry》2008,16(24):10236-10243
To search for new cruzain inhibitors, the synthesis of a series of novel 2-(N'-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines in a convergent manner is presented. The cruzain inhibitory activity of some of these compounds was evaluated and a binding model was proposed. All derivatives tested were active and the most significant inhibitory effect (80% at 100 microM) and IC(50) value (85 microM) were obtained from the 2-(N'-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine. Although further structural optimization to improve solubility is necessary, the molecular docking studies suggest that these inhibitors occupy the S2 pocket without irreversible enzyme inactivation, through hydrophobic interactions, thus, indicating a desirable mode of interaction for the design of novel inhibitors. 相似文献
240.
Burcelin R Uldry M Foretz M Perrin C Dacosta A Nenniger-Tosato M Seydoux J Cotecchia S Thorens B 《The Journal of biological chemistry》2004,279(2):1108-1115
To assess the role of the alpha1b-adrenergic receptor (AR) in glucose homeostasis, we investigated glucose metabolism in knockout mice deficient of this receptor subtype (alpha1b-AR-/-). Mutant mice had normal blood glucose and insulin levels, but elevated leptin concentrations in the fed state. During the transition to fasting, glucose and insulin blood concentrations remained markedly elevated for at least 6 h and returned to control levels after 24 h whereas leptin levels remained high at all times. Hyperinsulinemia in the post-absorptive phase was normalized by atropine or methylatropine indicating an elevated parasympathetic activity on the pancreatic beta cells, which was associated with increased levels of hypothalamic NPY mRNA. Euglycemic clamps at both low and high insulin infusion rates revealed whole body insulin resistance with reduced muscle glycogen synthesis and impaired suppression of endogenous glucose production at the low insulin infusion rate. The liver glycogen stores were 2-fold higher in the fed state in the alpha1b-AR-/- compared with control mice, but were mobilized at the same rate during the fed to fast transition or following glucagon injections. Finally, high fat feeding for one month increased glucose intolerance and body weight in the alpha1b-AR-/-, but not in control mice. Altogether, our results indicate that in the absence of the alpha1b-AR the expression of hypotalamic NPY and the parasympathetic nervous activity are both increased resulting in hyperinsulinemia and insulin resistance as well as favoring obesity and glucose intolerance development during high fat feeding. 相似文献