全文获取类型
收费全文 | 880篇 |
免费 | 68篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 25篇 |
2020年 | 8篇 |
2019年 | 13篇 |
2018年 | 22篇 |
2017年 | 23篇 |
2016年 | 28篇 |
2015年 | 47篇 |
2014年 | 42篇 |
2013年 | 50篇 |
2012年 | 68篇 |
2011年 | 67篇 |
2010年 | 34篇 |
2009年 | 30篇 |
2008年 | 57篇 |
2007年 | 57篇 |
2006年 | 44篇 |
2005年 | 60篇 |
2004年 | 38篇 |
2003年 | 44篇 |
2002年 | 39篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1972年 | 2篇 |
排序方式: 共有949条查询结果,搜索用时 15 毫秒
71.
A novel leptospiral protein increases ICAM-1 and E-selectin expression in human umbilical vein endothelial cells 总被引:2,自引:0,他引:2
Vieira ML D'Atri LP Schattner M Habarta AM Barbosa AS de Morais ZM Vasconcellos SA Abreu PA Gómez RM Nascimento AL 《FEMS microbiology letters》2007,276(2):172-180
It has been reported previously that activation of vascular endothelium by outer membrane proteins of the spirochetes Borrelia sp. and Treponema sp. resulted in enhanced expression of endothelial cell adhesion molecules. To investigate the role of leptospiral proteins in this process, a predicted lipoprotein encoded by the gene LIC10365 was selected, which belongs to a paralogous family that presents a domain of unknown function, DUF1565. The LIC10365 gene was cloned and the protein expressed in Escherichia coli C43 (DE3) strain using the vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and was used to assess its ability to activate cultured human umbilical vein endothelial cells. The rLIC10365 activated endothelium in such a manner that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose-dependent fashion. The LIC10365-encoded protein was identified in vivo in the renal tubules of animal during experimental infection with Leptospira interrogans. Collectively, these results implicate the LIC10365-coding protein of L. interrogans as a potential effector molecule in the promotion of a host inflammatory response. This is the first report of a leptospiral protein capable of up-regulating the expression of endothelial cell adhesion molecules ICAM-1 and E-selectin. 相似文献
72.
73.
74.
Gibberellic acid signaling is required for ambient temperature‐mediated induction of flowering in Arabidopsis thaliana 下载免费PDF全文
Vinicius Costa Galvão Silvio Collani Daniel Horrer Markus Schmid 《The Plant journal : for cell and molecular biology》2015,84(5):949-962
Distinct molecular mechanisms integrate changes in ambient temperature into the genetic pathways that govern flowering time in Arabidopsis thaliana. Temperature‐dependent eviction of the histone variant H2A.Z from nucleosomes has been suggested to facilitate the expression of FT by PIF4 at elevated ambient temperatures. Here we show that, in addition to PIF4, PIF3 and PIF5, but not PIF1 and PIF6, can promote flowering when expressed specifically in phloem companion cells (PCC), where they can induce FT and its close paralog, TSF. However, despite their strong potential to promote flowering, genetic analyses suggest that the PIF genes seem to have only a minor role in adjusting flowering in response to photoperiod or high ambient temperature. In addition, loss of PIF function only partially suppressed the early flowering phenotype and FT expression of the arp6 mutant, which is defective in H2A.Z deposition. In contrast, the chemical inhibition of gibberellic acid (GA) biosynthesis resulted in a strong attenuation of early flowering and FT expression in arp6. Furthermore, GA was able to induce flowering at low temperature (15°C) independently of FT, TSF, and the PIF genes, probably directly at the shoot apical meristem. Together, our results suggest that the timing of the floral transition in response to ambient temperature is more complex than previously thought and that GA signaling might play a crucial role in this process. 相似文献
75.
Ionta S Heydrich L Lenggenhager B Mouthon M Fornari E Chapuis D Gassert R Blanke O 《Neuron》2011,70(2):363-374
Self-consciousness has mostly been approached by philosophical enquiry and not by empirical neuroscientific study, leading to an overabundance of diverging theories and an absence of data-driven theories. Using robotic technology, we achieved specific bodily conflicts and induced predictable changes in a fundamental aspect of self-consciousness by altering where healthy subjects experienced themselves to be (self-location). Functional magnetic resonance imaging revealed that temporo-parietal junction (TPJ) activity reflected experimental changes in self-location that also depended on the first-person perspective due to visuo-tactile and visuo-vestibular conflicts. Moreover, in a large lesion analysis study of neurological patients with a well-defined state of abnormal self-location, brain damage was also localized at TPJ, providing causal evidence that TPJ encodes self-location. Our findings reveal that multisensory integration at the TPJ reflects one of the most fundamental subjective feelings of humans: the feeling of being an entity localized at a position in space and perceiving the world from this position and perspective. 相似文献
76.
77.
The aim of this work is to design and test an MRI probe (Gd-DOTAtyr-gal) able to report on the gene expression of β-galactosidase (β-Gal) in melanoma cells. The probe consists of a Gd-DOTA reporter bearing on its surface a tyrosine-galactose-pyranose functionality that, upon the release of the sugar moiety, readily transforms, in the presence of tyrosinase, into melanin oligomeric/polymeric mixture. The formation of Gd-DOTA-containing melanin oligomers and polymers is accompanied by a marked increase of the water proton relaxation rate. The steps involving the release of the galactose-pyranose group and the formation of the melanin-like structure have been carefully investigated in vitro by relaxometric and UV-vis measurements. Cellular uptake studies of Gd-DOTAtyr-gal by melanoma cells have shown that the probe enters the cells, and it appears not to be confined in endosomal vesicles. Using B16-F10LacZ transfected cells, the fast formation of paramagnetic melanin-Gd(III)-containing species has been assessed by the measurement of increased longitudinal relaxation rates of the cellular pellets suspensions. The in vitro results have been confirmed in in vivo MRI investigations on murine melanoma tumor bearing mice. Upon direct injection of Gd-DOTAtyr-gal, a good contrast is observed after 5 h post injection in B16-F10LacZ tumors, but not in B16-F10 tumors lacking the β-Gal enzyme. Gd-DOTAtyr-gal in combination with tyrosinase introduces a novel approach for the detection of β-Gal expression by MRI in vivo. 相似文献
78.
Diego Micheletti Michela Troggio Andrey Zharkikh Fabrizio Costa Mickael Malnoy Riccardo Velasco Silvio Salvi 《Tree Genetics & Genomes》2011,7(4):857-868
Knowledge about the sequence-based genetic diversity of a crop species is important in order to develop highly informative
genotyping assays, which will eventually positively impact breeding practice. Diversity data were obtained from two pools
of 185 and 75 accessions each, representing most of the species belonging to the genus Malus, by re-sequencing 27 gene-specific amplicons and by screening 237 Malus × domestica SNPs using the multiplex genotyping technology SNPlex™. Nucleotide diversity and insertion/deletion rates in M. × domestica were estimated as π = 0.0037 and 1/333 bp, respectively. The SNP frequency was estimated as 0.0194 (1 SNP/52 bp) while within a single apple
cultivar an average of one SNP in every 455 bp was found. We also investigated transferability (T
SNP) of the heterozygous state of SNPs across the species M. × domestica and the genus Malus. Raw re-sequencing showed that 12–15% of M. × domestica SNPs are transferable to a second M. × domestica cultivar, however T
SNP rose to ∼41% with SNPs selected for high minor allele frequency. T
SNP of chosen SNPs averaged ∼27% in the two M. × domestica-related species, Malus sieversii and Malus sylvestris, but was much lower in more distantly related species. On the basis of T
SNP, simulations, and empirical results, we calculated that a close-design, multiplexed genotyping array with at least 2,000
SNPs is required for building a highly saturated linkage maps within any M. × domestica cross. The same array would gradually lose informativeness in increasingly phylogenetically distant Malus species. 相似文献
79.
Filipecki AT Machado CJ Valle S Teixeira Mde O 《ILAR journal / National Research Council, Institute of Laboratory Animal Resources》2011,52(1):E8-15
Brazil has an exceptionally dynamic research sector in Latin America in health, biotechnology, and pharmacology, backed by defined government policies on science and technology and a health research agenda focusing on important neglected diseases: malaria, leishmaniasis, Chagas disease, turberculosis, leprosy, and dengue. The Brazilian health research policy promotes partnerships and networks among scientists in academic institutions in both wealthy industrialized and disease-endemic countries, and in these efforts the government's guidelines for animal use in biomedical research are considered fundamental to guarantee both animal welfare and the quality of research. Given international discussions of animal experimentation regulations and guidelines, in this article we describe current Brazilian legislation governing the use of animals in scientific investigations. We conclude that, despite advances in the implementation of the 3Rs (reduction, refinement, replacement), the new regulatory framework does not sufficiently incorporate ethical considerations, lacking explicit reference to the 3Rs as well as measures for their full application. The more humane use of animals in research will depend on the approach adopted by Brazil's National Council for the Control of Animal Experimentation to promote the 3Rs and to improve internal regulations as well as data collection and analysis in research institutions. In Brazil as elsewhere, one of the greatest challenges to policymakers is to harmonize the myriad and intertwined legal provisions without hindering biomedical research. 相似文献
80.