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211.
Upon contact with airway epithelial cells, mycobacteria activate several signal transduction events that are required for induction of NF-kappaB-dependent chemokine gene expression. However, downstream signaling pathways, especially that of Ca(2+)-dependent protein kinase C alpha (PKCalpha), and in particular, the identity of the IKKalphabeta signal pathway for CXCL8 secretion in Mycobacterium bovis BCG-induced epithelial cells are still unknown. In this study, we demonstrated that the phosphoinositide-phospholipase C (PI-PLC) downstream signaling pathway is involved in M. bovis BCG-induced CXCL8 release, since A549 cells pretreated with U73122, a PI-PLC inhibitor, inhibited CXCL8 release, whereas U73343 the inactive analog had no effect. In addition, our results demonstrated that M. bovis BCG-induced CXCL8 production by A549 cells was significantly blocked by using neomycin (another well-described inhibitor of PI-PLC with a different mechanism of action), Ro-32-0432 and Ro-31-8220 (two PKCalpha inhibitors), PP1 and PP2 (two potent and selective inhibitors of the Src-family tyrosine kinases), and Bay 11-7082 (an IkappaB phosphorylation inhibitor). We also demonstrated that M. bovis BCG can rapidly induce translocation of PKCalpha from the cytosol to the membrane, and that treatment of cells with M. bovis BCG caused time-dependent increases in phosphorylation of c-Src at tyrosine 416. Finally, our studies revealed that M. bovis BCG induced the association of c-Src and IKKalphabeta during the interaction of PKCalpha and IKKalphabeta. Altogether, these results represent the first evidence to date suggesting that M. bovis BCG activates the PI-PLC/PKCalpha/c-Src/IKKalphabeta signaling pathway to induce CXCL8 release in human epithelial cells. 相似文献
212.
In mammals, paternal and maternal pronuclei undergo profound chromatin reorganisation upon fertilisation. How these events
are orchestrated within centromeric regions to ensure proper chromosome segregation in the following cellular divisions is
unknown. In this study, we followed the dynamic unfolding of the centromeric regions, i.e. the centric and pericentric satellite
repeats, by DNA fluorescent in situ hybridization (FISH) during the first cell cycle up to the two-cell stage. The distinct
chromatin from female and male gametes both undergo rapid remodelling and reach a zygotic organisation in which the satellites
occupy restricted spatial domains surrounding the nucleolar precursor body. A transition from this zygotic to a somatic cell-like
organisation takes place during the two-cell stage. Using 3D immuno-FISH, we find that, whereas maternal pericentric regions
are marked with H3K9me3, H4K20me3 and HP1β, paternal ones only showed HP1β marking. Thus, despite different chromatin features,
male and female pronuclei organise their centromeric regions in the same way within the nuclei to align chromosomes on the
metaphase plate and segregate them appropriately. Our findings highlight the importance of ensuring a proper centromere function
while preserving the distinction of parental genome origin during the return to totipotency in the zygote.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
213.
Lecaudey V Ulloa E Anselme I Stedman A Schneider-Maunoury S Pujades C 《Developmental biology》2007,303(1):134-143
The vertebrate inner ear develops from an ectodermal placode adjacent to rhombomeres 4 to 6 of the segmented hindbrain. The placode then transforms into a vesicle and becomes regionalised along its anteroposterior, dorsoventral and mediolateral axes. To investigate the role of hindbrain signals in instructing otic vesicle regionalisation, we analysed ear development in zebrafish mutants for vhnf1, a gene expressed in the caudal hindbrain during otic induction and regionalisation. We show that, in vhnf1 homozygous embryos, the patterning of the otic vesicle is affected along both the anteroposterior and dorsoventral axes. First, anterior gene expression domains are either expanded along the whole anteroposterior axis of the vesicle or duplicated in the posterior region. Second, the dorsal domain is severely reduced, and cell groups normally located ventrally are shifted dorsally, sometimes forming a single dorsal patch along the whole AP extent of the otic vesicle. Third, and probably as a consequence, the size and organization of the sensory and neurogenic epithelia are disturbed. These results demonstrate that, in zebrafish, signals from the hindbrain control the patterning of the otic vesicle, not only along the anteroposterior axis, but also, as in amniotes, along the dorsoventral axis. They suggest that, despite the evolution of inner ear structure and function, some of the mechanisms underlying the regionalisation of the otic vesicle in fish and amniotes have been conserved. 相似文献
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216.
Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome
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Zipfel PF Edey M Heinen S Józsi M Richter H Misselwitz J Hoppe B Routledge D Strain L Hughes AE Goodship JA Licht C Goodship TH Skerka C 《PLoS genetics》2007,3(3):e41
Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H-related 1 (CFHR1) and complement factor H-related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of approximately 84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes. 相似文献
217.
de Jesus Santana Mayla Barbosa-Júnior Sebastião Martins Dias Lana Laene Lima Silva Lázara Aline Simões da Silva Givanildo Zildo Fortini Evandro Alexandre Batista Diego Silva Otoni Wagner Campos da Costa Netto Antônio Paulino Rocha Diego Ismael 《In vitro cellular & developmental biology. Plant》2022,58(6):865-875
In Vitro Cellular & Developmental Biology - Plant - The aim of this study was to establish a system of in vitro germination and propagation of Guazuma ulmifolia Lam. microcuttings (Malvaceae).... 相似文献
218.
Laura Remacha David Pirman Christopher E. Mahoney Javier Coloma Bruna Calsina Maria Currás-Freixes Rocío Letón Rafael Torres-Pérez Susan Richter Guillermo Pita Belén Herráez Giovanni Cianchetta Emiliano Honrado Lorena Maestre Miguel Urioste Javier Aller Óscar García-Uriarte María Ángeles Gálvez Alberto Cascón 《American journal of human genetics》2019,104(5):1008-1010
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Daniel F. Klessig Murli Manohar Shine Baby Aline Koch Wiseborn B. Danquah Emily Luna Hee‐Jin Park Judith M. Kolkman B. Gillian Turgeon Rebecca Nelson Jan E. Leach Valerie M. Williamson Karl‐Heinz Kogel Aardra Kachroo Frank C. Schroeder 《Journal of Phytopathology》2019,167(5):265-272
Recognition of specific molecule signatures of microbes, including pathogens, induces innate immune responses in plants, as well as in animals. Analogously, a nematode pheromone, the ascaroside ascr#18, induces hallmark plant defences including activation of (a) mitogen‐activated protein kinases, (b) salicylic acid‐ and jasmonic acid‐mediated defence signalling pathways and (c) defence gene expression and provides protection to a broad spectrum of pathogens. Ascr#18 is a member of an evolutionarily conserved family of nematode signalling molecules and is the major ascaroside secreted by plant–parasitic nematodes. Here, we report the effects of ascr#18 on resistance in four of the major economically important crops: maize, rice, wheat and soybean to some of their associated pathogens. Treatment with low nanomolar to low micromolar concentrations of ascr#18 provided from partial to strong protection in seven of eight plant–pathogen systems tested with viruses, bacteria, fungi, oomycetes and nematodes. This research may have potential to improve agricultural sustainability by reducing use of potentially harmful agrochemicals and enhance food security worldwide. 相似文献