全文获取类型
收费全文 | 458篇 |
免费 | 45篇 |
出版年
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 4篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 18篇 |
2012年 | 17篇 |
2011年 | 25篇 |
2010年 | 32篇 |
2009年 | 22篇 |
2008年 | 10篇 |
2007年 | 8篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 6篇 |
2003年 | 12篇 |
2002年 | 14篇 |
2001年 | 13篇 |
2000年 | 15篇 |
1999年 | 17篇 |
1998年 | 13篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1968年 | 3篇 |
1967年 | 5篇 |
排序方式: 共有503条查询结果,搜索用时 15 毫秒
51.
Tamminga C Sedegah M Regis D Chuang I Epstein JE Spring M Mendoza-Silveiras J McGrath S Maiolatesi S Reyes S Steinbeiss V Fedders C Smith K House B Ganeshan H Lejano J Abot E Banania GJ Sayo R Farooq F Belmonte M Murphy J Komisar J Williams J Shi M Brambilla D Manohar N Richie NO Wood C Limbach K Patterson NB Bruder JT Doolan DL King CR Diggs C Soisson L Carucci D Levine G Dutta S Hollingdale MR Ockenhouse CF Richie TL 《PloS one》2011,6(10):e25868
Background
A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.Methodology/Principal Findings
NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.Significance
The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection.Trial Registration
ClinicalTrials.gov NCT00392015相似文献52.
Sedegah M Tamminga C McGrath S House B Ganeshan H Lejano J Abot E Banania GJ Sayo R Farooq F Belmonte M Manohar N Richie NO Wood C Long CA Regis D Williams FT Shi M Chuang I Spring M Epstein JE Mendoza-Silveiras J Limbach K Patterson NB Bruder JT Doolan DL King CR Soisson L Diggs C Carucci D Dutta S Hollingdale MR Ockenhouse CF Richie TL 《PloS one》2011,6(10):e24586
53.
Pauly C Spring P Gahan D O'Doherty JV 《Animal : an international journal of animal bioscience》2011,5(3):378-386
A 2 × 2 factorial experiment was conducted to investigate the effects of cereal type (barley v. oat) and exogenous enzyme supplementation (with or without) on intestinal fermentation, and on indole and skatole levels in the intestinal content and the adipose tissue in finisher boars. The experimental treatments were as follows: (i) barley-based diet, (ii) barley-based diet with enzyme supplement, (iii) oat-based diet and (iv) oat-based diet with enzyme supplement. The enzyme supplement contained endo-1,3(4)-β-glucanase (EC 3.2.1.6) and endo-1,4-β-xylanase (EC 3.2.1.8). The animals were fed ad libitum for 45 days from 76.0 to 113.6 kg live weight. Feeding barley-based diets led to higher (P < 0.05) total volatile fatty acids concentrations in the large intestine. Proportions of propionic- and butyric-acids were higher and that of acetic acid lower in digesta from barley-based in comparison to oat-based diets (P < 0.001). Consequently, pH in the large intestine was higher after feeding oat-based in comparison to barley-based diets. Animals fed unsupplemented oat-based diet had higher (P < 0.01) indole concentrations in the digesta from the proximal colon than those fed barley-based diets. Feeding oat-based diets led to lower (P < 0.01) skatole and higher (P < 0.001) indole concentrations in the digesta from the terminal colon than barley-based diets. skatole concentrations in the adipose tissue did not differ (P > 0.05) between the experimental treatments. Pigs offered the barley-based diets had lower (P < 0.001) indole concentrations in the adipose tissue compared with those fed the oat-based diet. In conclusion, barley-based diets were more efficient than oat-based diets in limiting concentrations of indole in the adipose tissue. 相似文献
54.
55.
Welch M Mikkelsen H Swatton JE Smith D Thomas GL Glansdorp FG Spring DR 《Molecular bioSystems》2005,1(3):196-202
Over the last decade or so, a wealth of research has established that bacteria communicate with one another using small molecules. These signals enable the individuals in a population to coordinate their behaviour. In the case of pathogens, this behaviour may include decisions such as when to attack a host organism or form a biofilm. Consequently, such signalling systems are excellent targets for the development of new antibacterial therapies. In this review, we assess how Gram-negative bacteria use small molecules for cell-cell communication, and discuss the main approaches that have been developed to interfere with it. 相似文献
56.
57.
Novel Thermophilic Sulfate-Reducing Bacteria from a Geothermally Active Underground Mine in Japan 总被引:1,自引:0,他引:1 下载免费PDF全文
Anna H. Kaksonen Jason J. Plumb Wendy J. Robertson Stefan Spring Peter Schumann Peter D. Franzmann Jaakko A. Puhakka 《Applied microbiology》2006,72(5):3759-3762
Thermophilic sulfate-reducing bacteria were enriched from samples obtained from a geothermal underground mine in Japan. The enrichment cultures contained bacteria affiliated with the genera Desulfotomaculum, Thermanaeromonas, Thermincola, Thermovenabulum, Moorella, “Natronoanaerobium,” and Clostridium. Two novel thermophilic sulfate-reducing strains, RL50JIII and RL80JIV, affiliated with the genera Desulfotomaculum and Thermanaeromonas, respectively, were isolated. 相似文献
58.
Al-Sukhni W Joe S Lionel AC Zwingerman N Zogopoulos G Marshall CR Borgida A Holter S Gropper A Moore S Bondy M Klein AP Petersen GM Rabe KG Schwartz AG Syngal S Scherer SW Gallinger S 《Human genetics》2012,131(9):1481-1494
Adenocarcinoma of the pancreas is a significant cause of cancer mortality, and up to 10?% of cases appear to be familial. Heritable genomic copy number variants (CNVs) can modulate gene expression and predispose to disease. Here, we identify candidate predisposition genes for familial pancreatic cancer (FPC) by analyzing germline losses or gains present in one or more high-risk patients and absent in a large control group. A total of 120 FPC cases and 1,194 controls were genotyped on the Affymetrix 500K array, and 36 cases and 2,357 controls were genotyped on the Affymetrix 6.0 array. Detection of CNVs was performed by multiple computational algorithms and partially validated by quantitative PCR. We found no significant difference in the germline CNV profiles of cases and controls. A total of 93 non-redundant FPC-specific CNVs (53 losses and 40 gains) were identified in 50 cases, each CNV present in a single individual. FPC-specific CNVs overlapped the coding region of 88 RefSeq genes. Several of these genes have been reported to be differentially expressed and/or affected by copy number alterations in pancreatic adenocarcinoma. Further investigation in high-risk subjects may elucidate the role of one or more of these genes in genetic predisposition to pancreatic cancer. 相似文献
59.
I Anderson E Saunders A Lapidus M Nolan S Lucas H Tice TG Del Rio JF Cheng C Han R Tapia LA Goodwin S Pitluck K Liolios K Mavromatis I Pagani N Ivanova N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser CD Jeffries YJ Chang EM Brambilla M Rohde S Spring M Göker JC Detter T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk 《Standards in genomic sciences》2012,6(2):155-164
Thermodesulfatator indicus Moussard et al. 2004 is a member of the Thermodesulfobacteriaceae, a family in the phylum Thermodesulfobacteria that is currently poorly characterized at the genome level. Members of this phylum are of interest because they represent a distinct, deep-branching, Gram-negative lineage. T. indicus is an anaerobic, thermophilic, chemolithoautotrophic sulfate reducer isolated from a deep-sea hydrothermal vent. Here we describe the features of this organism, together with the complete genome sequence, and annotation. The 2,322,224 bp long chromosome with its 2,233 protein-coding and 58 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
60.
B Abt C Han C Scheuner M Lu A Lapidus M Nolan S Lucas N Hammon S Deshpande JF Cheng R Tapia LA Goodwin S Pitluck K Liolios I Pagani N Ivanova K Mavromatis N Mikhailova M Huntemann A Pati A Chen K Palaniappan M Land L Hauser EM Brambilla M Rohde S Spring S Gronow M Göker T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk JC Detter 《Standards in genomic sciences》2012,6(2):194-209
Spirochaeta coccoides Dröge et al. 2006 is a member of the genus Spirochaeta Ehrenberg 1835, one of the oldest named genera within the Bacteria. S. coccoides is an obligately anaerobic, Gram-negative, non-motile, spherical bacterium that was isolated from the hindgut contents of the termite Neotermes castaneus. The species is of interest because it may play an important role in the digestion of breakdown products from cellulose and hemicellulose in the termite gut. Here we provide a taxonomic re-evaluation for strain SPN1T, and based on physiological and genomic characteristics, we propose its reclassification as a novel species in the genus Sphaerochaeta, a recently published sister group of the Spirochaeta. The 2,227,296 bp long genome of strain SPN1T with its 1,866 protein-coding and 58 RNA genes is a part of the Genomic
Encyclopedia of
Bacteria and
Archaea project. 相似文献