全文获取类型
收费全文 | 372篇 |
免费 | 35篇 |
出版年
2021年 | 4篇 |
2020年 | 7篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 20篇 |
2012年 | 8篇 |
2011年 | 9篇 |
2010年 | 10篇 |
2009年 | 14篇 |
2008年 | 15篇 |
2007年 | 14篇 |
2006年 | 21篇 |
2005年 | 6篇 |
2004年 | 7篇 |
2003年 | 13篇 |
2002年 | 14篇 |
2001年 | 16篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 7篇 |
1995年 | 10篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1986年 | 4篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 8篇 |
1980年 | 2篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 9篇 |
1973年 | 4篇 |
1971年 | 2篇 |
1970年 | 7篇 |
1969年 | 4篇 |
1967年 | 2篇 |
1966年 | 5篇 |
排序方式: 共有407条查询结果,搜索用时 15 毫秒
61.
1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI) 总被引:4,自引:0,他引:4
Heerding DA Chan G DeWolf WE Fosberry AP Janson CA Jaworski DD McManus E Miller WH Moore TD Payne DJ Qiu X Rittenhouse SF Slater-Radosti C Smith W Takata DT Vaidya KS Yuan CC Huffman WF 《Bioorganic & medicinal chemistry letters》2001,11(16):2061-2065
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI. 相似文献
62.
Shelly J. Krebs Sean P. McBurney Dina N. Kovarik Chelsea D. Waddell J. Pablo Jaworski William F. Sutton Michelle M. Gomes Maria Trovato Garret Waagmeester Susan J. Barnett Piergiuseppe DeBerardinis Nancy L. Haigwood 《PloS one》2014,9(12)
Developing a vaccine that overcomes the diversity of HIV-1 is likely to require a strategy that directs antibody (Ab) responses toward conserved regions of the viral Envelope (Env). However, the generation of neutralizing Abs (NAbs) targeting these regions through vaccination has proven to be difficult. One conserved region of particular interest is the membrane proximal external region (MPER) of Env located within the gp41 ectodomain. In order to direct the immune response to this region, the MPER and gp41 ectodomain were expressed separately as N-terminal fusions to the E2 protein of Geobacillus stearothermophilus. The E2 protein acts as a scaffold by self-assembling into 60-mer particles, displaying up to 60 copies of the fused target on the surface. Rabbits were immunized with E2 particles displaying MPER and/or the gp41 ectodomain in conjunction with DNA encoding full-length gp160. Only vaccines including E2 particles displaying MPER elicited MPER-specific Ab responses. NAbs were elicited after two immunizations that largely targeted the V3 loop. To overcome V3 immunodominance in the DNA component, E2 particles displaying MPER were used in conjunction with gp160 DNA lacking hypervariable regions V2, V3, or combined V1V2V3. All rabbits had HIV binding Ab responses and NAbs following the second vaccination. Using HIV-2/HIV-1 MPER chimeric viruses as targets, NAbs were detected in 12/16 rabbits after three immunizations. Low levels of NAbs specific for Tier 1 and 2 viruses were observed in all groups. This study provides evidence that co-immunizing E2 particles displaying MPER and gp160 DNA can focus Ab responses toward conserved regions of Env. 相似文献
63.
Rafał Donczew Thorsten Mielke Paweł Jaworski Jolanta Zakrzewska-Czerwińska Anna Zawilak-Pawlik 《Journal of molecular biology》2014
In bacteria, chromosome replication is initiated by binding of the DnaA initiator protein to DnaA boxes located in the origin of chromosomal replication (oriC). This leads to DNA helix opening within the DNA-unwinding element. Helicobacter pylori oriC, the first bipartite origin identified in Gram-negative bacteria, contains two subregions, oriC1 and oriC2, flanking the dnaA gene. The DNA-unwinding element region is localized in the oriC2 subregion downstream of dnaA. Surprisingly, oriC2–DnaA interactions were shown to depend on DNA topology, which is unusual in bacteria but is similar to initiator–origin interactions observed in higher organisms. In this work, we identified three DnaA boxes in the oriC2 subregion, two of which were bound only as supercoiled DNA. We found that all three DnaA boxes play important roles in orisome assembly and subsequent DNA unwinding, but different functions can be assigned to individual boxes. This suggests that the H. pylori oriC may be functionally divided, similar to what was described recently for Escherichia coli oriC. On the basis of these results, we propose a model of initiation complex formation in H. pylori. 相似文献
64.
Eike Steinig Sebastin Duchêne Izzard Aglua Andrew Greenhill Rebecca Ford Mition Yoannes Jan Jaworski Jimmy Drekore Bohu Urakoko Harry Poka Clive Wurr Eri Ebos David Nangen Laurens Manning Moses Laman Cadhla Firth Simon Smith William Pomat Steven Y C Tong Lachlan Coin Emma McBryde Paul Horwood 《Molecular biology and evolution》2022,39(3)
Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354–1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth–death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG. 相似文献
65.
66.
On association in a copula with time transformations 总被引:2,自引:0,他引:2
67.
68.
69.
70.