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排序方式: 共有535条查询结果,搜索用时 171 毫秒
51.
Lamarre D Anderson PC Bailey M Beaulieu P Bolger G Bonneau P Bös M Cameron DR Cartier M Cordingley MG Faucher AM Goudreau N Kawai SH Kukolj G Lagacé L LaPlante SR Narjes H Poupart MA Rancourt J Sentjens RE St George R Simoneau B Steinmann G Thibeault D Tsantrizos YS Weldon SM Yong CL Llinàs-Brunet M 《Nature》2003,426(6963):186-189
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics. 相似文献
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Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献
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Floyd JA Gold DA Concepcion D Poon TH Wang X Keithley E Chen D Ward EJ Chinn SB Friedman RA Yu HT Moriwaki K Shiroishi T Hamilton BA 《Nature genetics》2003,35(3):221-228
Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. 相似文献
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Quantitative epigenetics 总被引:4,自引:0,他引:4
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Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia 总被引:3,自引:0,他引:3
Pollock PM Cohen-Solal K Sood R Namkoong J Martino JJ Koganti A Zhu H Robbins C Makalowska I Shin SS Marin Y Roberts KG Yudt LM Chen A Cheng J Incao A Pinkett HW Graham CL Dunn K Crespo-Carbone SM Mackason KR Ryan KB Sinsimer D Goydos J Reuhl KR Eckhaus M Meltzer PS Pavan WJ Trent JM Chen S 《Nature genetics》2003,34(1):108-112
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