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141.
SE Ward HS Kim K Komurov S Mendiratta PL Tsai M Schmolke N Satterly B Manicassamy CV Forst MG Roth A García-Sastre KM Blazewska CE McKenna BM Fontoura MA White 《PloS one》2012,7(8):e39284
Influenza A virus infects 5-20% of the population annually, resulting in ~35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors. 相似文献
142.
Zamira A. Ávila-Valle Alondra Castro-Campillo Livia León-Paniagua Isaías H. Salgado-Ugalde Adolfo G. Navarro-Sigüenza Blanca E. Hernández-Baños José Ramírez-Pulido 《Mammalian Biology》2012,77(3):166-177
Several authors have discussed whether Peromyscus furvus is a monotypic species rather than a polytypic entity, that it includes more than one species. Here, we analyze these questions by means of traditional morphometrics and by genetic analyses using ND3-ND4 mtDNA genes as markers. In spite of a generalized overlap of the measurable characters among populations, our analyses show that the northernmost populations, which was assignable to P. latirostris, consistently show larger dimensions overall. The amount of genetic differentiation revealed by our molecular data, support conclusive evidence to suggest this taxon is a valid species. Our results also disclose that morphometric and molecular segregation between P. furvus and P. angustirostris is still incomplete. Finally, the two populations from the state of Oaxaca showed more morphometric affinity with those attributable to P. furvus and revealed a discrete degree of genetic differentiation. Nevertheless, their systematic position is not clear yet. 相似文献
143.
144.
Ricardo Rajsbaum Randy A. Albrecht May K. Wang Natalya P. Maharaj Gijs A. Versteeg Estanislao Nistal-Villán Adolfo García-Sastre Michaela U. Gack 《PLoS pathogens》2012,8(11)
Influenza A viruses can adapt to new host species, leading to the emergence of novel pathogenic strains. There is evidence that highly pathogenic viruses encode for non-structural 1 (NS1) proteins that are more efficient in suppressing the host immune response. The NS1 protein inhibits type-I interferon (IFN) production partly by blocking the TRIM25 ubiquitin E3 ligase-mediated Lys63-linked ubiquitination of the viral RNA sensor RIG-I, required for its optimal downstream signaling. In order to understand possible mechanisms of viral adaptation and host tropism, we examined the ability of NS1 encoded by human (Cal04), avian (HK156), swine (SwTx98) and mouse-adapted (PR8) influenza viruses to interact with TRIM25 orthologues from mammalian and avian species. Using co-immunoprecipitation assays we show that human TRIM25 binds to all tested NS1 proteins, whereas the chicken TRIM25 ortholog binds preferentially to the NS1 from the avian virus. Strikingly, none of the NS1 proteins were able to bind mouse TRIM25. Since NS1 can inhibit IFN production in mouse, we tested the impact of TRIM25 and NS1 on RIG-I ubiquitination in mouse cells. While NS1 efficiently suppressed human TRIM25-dependent ubiquitination of RIG-I 2CARD, NS1 inhibited the ubiquitination of full-length mouse RIG-I in a mouse TRIM25-independent manner. Therefore, we tested if the ubiquitin E3 ligase Riplet, which has also been shown to ubiquitinate RIG-I, interacts with NS1. We found that NS1 binds mouse Riplet and inhibits its activity to induce IFN-β in murine cells. Furthermore, NS1 proteins of human but not swine or avian viruses were able to interact with human Riplet, thereby suppressing RIG-I ubiquitination. In conclusion, our results indicate that influenza NS1 protein targets TRIM25 and Riplet ubiquitin E3 ligases in a species-specific manner for the inhibition of RIG-I ubiquitination and antiviral IFN production. 相似文献
145.
Guillermo Velo-Antón Mario García-París Adolfo Cordero Rivera 《Conservation Genetics》2008,9(5):1263-1274
The European pond turtle (Emys orbicularis) is threatened and in decline in several regions of its natural range, due to habitat loss combined with population fragmentation.
In this work, we have focused our efforts on studying the genetic diversity and structure of Iberian populations with a fine-scale
sampling (254 turtles in 10 populations) and a representation from North Africa and Balearic island populations. Using both
nuclear and mitochondrial markers (seven microsatellites, ∼1048 bp nDNA and ∼1500 bp mtDNA) we have carried out phylogenetic
and demographic analyses. Our results show low values of genetic diversity at the mitochondrial level although our microsatellite
dataset revealed relatively high levels of genetic variability with a latitudinal genetic trend decreasing from southern to
northern populations. A moderate degree of genetic differentiation was estimated for Iberian populations (genetic distances,
F
ST
values and clusters in the Bayesian analysis). The results in this study combining mtDNA and nDNA, provide the most comprehensive
population genetic data for E. orbicularis in the Iberian Peninsula. Our results suggest that Iberian populations within the Iberian–Moroccan lineage should be considered
as a single subspecies with five management units, and emphasize the importance of habitat management rather than population
reinforcement (i.e. captive breeding and reintroduction) in this long-lived species. 相似文献
146.
Catalina Monzón-Argüello Joaquín Muñoz Adolfo Marco Luis Felipe López-Jurado Ciro Rico 《Conservation Genetics》2008,9(4):1045-1049
We describe 12 new polymorphic dinucleotide microsatellite loci and multiplex Polymerase Chain Reaction conditions from the
loggerhead sea turtle Caretta caretta. Levels of polymorphism were assessed in 50 individuals from the nesting population of the Cape Verde Islands. Number of
alleles ranged from 3 to 13 (average of 7.33) and the values of observed heterozygosities from 0.32 to 0.80 (average of 0.61).
Cross-species amplification on three other marine turtles, Chelonia mydas, Eretmochelys imbricata and Dermochelys coriacea, revealed polymorphism and variability at eight, eleven and three loci, respectively. 相似文献
147.
Takaaki Nakaya Jerome Cros Man-Seong Park Yurie Nakaya Hongyong Zheng Ana Sagrera Enrique Villar Adolfo García-Sastre Peter Palese 《Journal of virology》2001,75(23):11868-11873
A complete cDNA clone of the Newcastle disease virus (NDV) vaccine strain Hitchner B1 was constructed, and infectious recombinant virus expressing an influenza virus hemagglutinin was generated by reverse genetics. The rescued virus induces a strong humoral antibody response against influenza virus and provides complete protection against a lethal dose of influenza virus challenge in mice, demonstrating the potential of recombinant NDV as a vaccine vector. 相似文献
148.
Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q 总被引:6,自引:0,他引:6
Alex Desautels Gustavo Turecki Jacques Montplaisir Adolfo Sequeira Andrei Verner Guy A. Rouleau 《American journal of human genetics》2001,69(6):1266-1270
Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction.05; P=6x10(-4); autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS. 相似文献
149.
Flaminia Cesare Marincola Mariano Casu Giuseppe Saba Adolfo Lai Pompea del Vecchio Guido Barone 《International journal of biological macromolecules》2001,29(4-5)
The 23Na NMR quadrupolar relaxation in NaDNA aqueous solutions has been investigated in the presence of
(+) and
(−) arabitol. Quite different results were produced by the enantiomers, i.e. the addition of
(+) arabitol produced a small increase of the 23Na NMR relaxation rates, while in the presence of
(−) arabitol a significant decrease was observed. These findings were analysed and discussed in terms of an effective interaction of
(−) arabitol with DNA. 相似文献
150.