全文获取类型
收费全文 | 1574篇 |
免费 | 130篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 26篇 |
2021年 | 53篇 |
2020年 | 52篇 |
2019年 | 49篇 |
2018年 | 53篇 |
2017年 | 63篇 |
2016年 | 72篇 |
2015年 | 102篇 |
2014年 | 136篇 |
2013年 | 129篇 |
2012年 | 169篇 |
2011年 | 105篇 |
2010年 | 90篇 |
2009年 | 68篇 |
2008年 | 93篇 |
2007年 | 80篇 |
2006年 | 69篇 |
2005年 | 57篇 |
2004年 | 40篇 |
2003年 | 45篇 |
2002年 | 30篇 |
2001年 | 11篇 |
1999年 | 12篇 |
1998年 | 12篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 8篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有1704条查询结果,搜索用时 15 毫秒
71.
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
72.
73.
74.
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
75.
76.
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
77.
Alexandra N. Myers Sara D. Lawhon Alison B. Diesel Charles W. Bradley Aline Rodrigues Hoffmann William J. Murphy Lives Cat Genome Consortium 《PLoS genetics》2022,18(2)
Dermatophytosis, also known as ringworm, is a contagious fungal skin disease affecting humans and animals worldwide. Persian cats exhibit severe forms of the disease more commonly than other breeds of cat, including other long-haired breeds. Certain types of severe dermatophytosis in humans are reportedly caused by monogenic inborn errors of immunity. The goal of this study was to identify genetic variants in Persian cats contributing to the phenotype of severe dermatophytosis. Whole-genome sequencing of case and control Persian cats followed by a genome-wide association study identified a highly divergent, disease-associated haplotype on chromosome F1 containing the S100 family of genes. S100 calcium binding protein A9 (S100A9), which encodes a subunit of the antimicrobial heterodimer known as calprotectin, contained 13 nonsynonymous variants between cases and controls. Evolutionary analysis of S100A9 haplotypes comparing cases, controls, and wild felids suggested the divergent disease-associated haplotype was likely introgressed into the domestic cat lineage and maintained via balancing selection. We demonstrated marked upregulation of calprotectin expression in the feline epidermis during dermatophytosis, suggesting involvement in disease pathogenesis. Given this divergent allele has been maintained in domestic cat and wildcat populations, this haplotype may have beneficial effects against other pathogens. The pathogen specificity of this altered protein should be investigated before attempting to reduce the allele frequency in the Persian cat breed. Further work is needed to clarify if severe Persian dermatophytosis is a monogenic disease or if hidden disease-susceptibility loci remain to be discovered. Consideration should be given to engineering antimicrobial peptides such as calprotectin for topical treatment of dermatophytosis in humans and animals. 相似文献
78.
Maria Florencia Tellechea Flvia S. Donaires Vinícius S. de Carvalho Brbara A. Santana Fernanda B. da Silva Raissa S. Tristo Lílian F. Moreira Aline F. de Souza Yordanka M. Armenteros Lygia V. Pereira Rodrigo T. Calado 《Cell death & disease》2022,13(4)
In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.Subject terms: Anaemia, Induced pluripotent stem cells 相似文献
79.
Markus A. Altmeyer Aline Marschner Rolf Schiffmann Christian D. Klein 《Bioorganic & medicinal chemistry letters》2010,20(14):4038-4044
Inhibitors of methionine aminopeptidases (MetAPs) are treatment options for various pathological conditions. Several inhibitor classes have been described previously, but only few data on the subtype selectivity, which is of crucial importance for these enzymes, is available. We present a systematic study on the subtype- and species-selectivity of MetAP inhibitors that require the binding of an auxiliary metal ion. This includes, in particular, compounds based on the benzimidazole pharmacophore, but also hydroxyquinoline and picolinic acid derivatives. Our data indicates that a significant degree of selectivity can be attained with metal-dependent MetAP inhibitors. 相似文献
80.
Potentials and limitations of histone repeat sequences for phylogenetic reconstruction of Sophophora. 总被引:1,自引:0,他引:1
Simplified DNA sequence acquisition has provided many new data sets that are useful for phylogenetic reconstruction, including single- and multiple-copy nuclear and organellar genes. Although transcribed regions receive much attention, nontranscribed regions have recently been added to the repertoire of sequences suitable for phylogenetic studies, especially for closely related taxa. We evaluated the efficacy of a small portion of the histone repeat for phylogenetic reconstruction among Drosophila species. Histone repeats in invertebrates offer distinct advantages similar to those of widely used ribosomal repeats. First, the units are tandemly repeated and undergo concerted evolution. Second, histone repeats include both highly conserved coding and variable intergenic regions. This composition facilitates application of "universal" primers spanning potentially informative sites. We examined a small region of the histone repeat, including the intergenic spacer segments of coding regions from the divergently transcribed H2A and H2B histone genes. The spacer (about 230 bp) exists as a mosaic with highly conserved functional motifs interspersed with rapidly diverging regions; the former aid in alignment of the spacer. There are no ambiguities in alignment of coding regions. Coding and noncoding regions were analyzed together and separately for phylogenetic information. Parsimony, distance, and maximum-likelihood methods successfully retrieve the corroborated phylogeny for the taxa examined. This study demonstrates the resolving power of a small histone region which may now be added to the growing collection of phylogenetically useful DNA sequences. 相似文献