全文获取类型
收费全文 | 1088篇 |
免费 | 64篇 |
专业分类
1152篇 |
出版年
2024年 | 3篇 |
2023年 | 11篇 |
2022年 | 28篇 |
2021年 | 64篇 |
2020年 | 29篇 |
2019年 | 28篇 |
2018年 | 30篇 |
2017年 | 30篇 |
2016年 | 49篇 |
2015年 | 76篇 |
2014年 | 78篇 |
2013年 | 77篇 |
2012年 | 91篇 |
2011年 | 95篇 |
2010年 | 55篇 |
2009年 | 48篇 |
2008年 | 43篇 |
2007年 | 59篇 |
2006年 | 35篇 |
2005年 | 38篇 |
2004年 | 40篇 |
2003年 | 39篇 |
2002年 | 28篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 11篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1152条查询结果,搜索用时 0 毫秒
21.
Henar Hernando Claire Shannon-Lowe Abul B Islam Fatima Al-Shahrour Javier Rodríguez-Ubreva Virginia C Rodríguez-Cortez Biola M Javierre Cristina Mangas Agustín F Fernández Maribel Parra Henri-Jacques Delecluse Manel Esteller Eduardo López-Granados Mario F Fraga Nuria López-Bigas Esteban Ballestar 《Genome biology》2013,14(1):R3
22.
Geoffrey S. Gottlieb Robert A. Smith Ndeye Mery Dia Badiane Selly Ba Stephen E. Hawes Macoumba Toure Alison K. Starling Fatou Traore Fatima Sall Stephen L. Cherne Joshua Stern Kim G. Wong Paul Lu Moon Kim Dana N. Raugi Airin Lam James I. Mullins Nancy B. Kiviat Papa Salif Sow for the UW-Dakar HIV- Study Group 《PloS one》2011,6(7)
Background
Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.Methods
We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.Results
No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Conclusion
Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients. 相似文献23.
Purification,Characterization and Antibacterial Activity of l‐amino Acid Oxidase from Cerastes cerastes 下载免费PDF全文
Ziad‐Meziane Hanane‐Fadila Laraba‐Djebari Fatima 《Journal of biochemical and molecular toxicology》2014,28(8):347-354
Antibiotic resistance presents a real problem in which new antibacterial molecules from natural secretions could be beneficial in the development of new drugs. In this study, Cerastes cerastes venom was investigated for its antibacterial activity against Gram‐positive and Gram‐negative bacteria. The antibacterial activity was evaluated by measuring the halo inhibition and minimum inhibitory concentration (MIC). An l ‐amino acid oxidase (CcLAAO) was purified from this venom using three chromatographic steps; its homogeneity (60 kDa) was confirmed by SDS‐PAGE. LC–MS/MS analysis of CcLAAO showed similarities with other LAAO enzymes from Echis ocellatus and Viridovipera stejnegeri venoms. CcLAAO presents an antibacterial activity against three bacterial strains (Staphylococcus aureus, Methicillin‐resistant S. aureus, and Pseudomonas aeruginosa) with MIC values of 10, 10, and 20 μg/mL, respectively. However, no effect was observed against Escherichia coli and yeast strains. Kinetic parameters of CcLAAO evaluated on l ‐leucine at pH 8.0 and 20°C were Km = 0.06 mmol and Vmax = 164 mmol/min. 相似文献
24.
Kathryn L. Hopkins Fatima Laher Kennedy Otwombe Gavin Churchyard Linda-Gail Bekker Stephen DeRosa Maphoshane Nchabeleng Koleka Mlisana James Kublin Glenda Gray 《PloS one》2014,9(8)
Background
Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses.Methods
Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors.Results
Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4–27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500).Conclusions
Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity). 相似文献25.
26.
da Silva K Florentino LA da Silva KB de Brandt E Vandamme P de Souza Moreira FM 《Systematic and applied microbiology》2012,35(3):175-182
The aim of the present study was to identify a collection of 35 Cupriavidus isolates at the species level and to examine their capacity to nodulate and fix N(2). These isolates were previously obtained from the root nodules of two promiscuous trap species, Phaseolus vulgaris and Leucaena leucocephala, inoculated with soil samples collected near Sesbania virgata plants growing in Minas Gerais (Brazil) pastures. Phenotypic and genotypic methods applied for this study were SDS-PAGE of whole-cell proteins, and 16S rRNA and gyrB gene sequencing. To confirm the ability to nodulate and fix N(2), the presence of the nodC and nifH genes was also determined, and an experiment was carried out with two representative isolates in order to authenticate them as legume nodule symbionts. All 35 isolates belonged to the betaproteobacterium Cupriavidus necator, they possessed the nodC and nifH genes, and two representative isolates were able to nodulate five different promiscuous legume species: Mimosa caesalpiniaefolia, L. leucocephala, Macroptilium atropurpureum, P. vulgaris and Vigna unguiculata. This is the first study to demonstrate that C. necator can nodulate legume species. 相似文献
27.
Enam Fatima Mansell Thomas J. 《Journal of industrial microbiology & biotechnology》2019,46(9-10):1445-1459
Journal of Industrial Microbiology & Biotechnology - The human gut is an ecosystem comprising trillions of microbes interacting with the host. The composition of the microbiota and their... 相似文献
28.
Trombetta IC Batalha LT Rondon MU Laterza MC Kuniyoshi FH Gowdak MM Barretto AC Halpern A Villares SM Negrão CE 《American journal of physiology. Heart and circulatory physiology》2003,285(3):H974-H982
We studied the effects of a hypocaloric diet (D, n = 24, age: 32.2 +/- 1.4 yr, body mass index: 34.7 +/- 0.5 kg/m2) and a hypocaloric diet associated with exercise training (D + T, n = 25, age: 32.3 +/- 1.3 yr, body mass index: 32.9 +/- 0.4 kg/m2) on muscle metaboreflex control, muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, and forearm blood flow (plethysmography) levels during handgrip exercise at 10% and 30% of maximal voluntary contraction in normotensive obese women. An additional 10 women matched by age and body mass index were studied as a nonadherent group. D or D + T significantly decreased body mass index. D or D + T significantly decreased resting MSNA (bursts/100 heartbeats). The absolute levels of MSNA were significantly lower throughout 10% and 30% exercise after D or D + T, although no change was found in the magnitude of response of MSNA. D + T, but not D, significantly increased resting forearm vascular conductance. D + T significantly increased the magnitude of the response of forearm vascular conductance during 30% exercise. D or D + T significantly increased MSNA levels during posthandgrip circulatory arrest when muscle metaboreflex is isolated. In conclusion, weight loss improves muscle metaboreflex control in obese women. Weight loss reduces MSNA, which seems to be centrally mediated. Weight loss by D + T increases forearm vascular conductance at rest and during exercise in obese individuals. 相似文献
29.
Parthenolide sensitizes cells to X-ray-induced cell killing through inhibition of NF-kappaB and split-dose repair 总被引:2,自引:0,他引:2
Mendonca MS Chin-Sinex H Gomez-Millan J Datzman N Hardacre M Comerford K Nakshatri H Nye M Benjamin L Mehta S Patino F Sweeney C 《Radiation research》2007,168(6):689-697
Human cancers have multiple alterations in cell signaling pathways that promote resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene lactone that has been shown to inhibit several pro-survival cell signaling pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We investigated whether parthenolide would enhance X-ray-induced cell killing in radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell growth, reduced plating efficiency, and induced apoptosis through stabilization of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X-ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S-phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and G2/M blocks, but depletion of radioresistant S-phase cells does not explain the observed X-ray sensitization. Further studies demonstrated that the enhancement of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose repair. 相似文献
30.
Regulation of clinical research and bioethics in Portugal 总被引:1,自引:0,他引:1
Carvalho FL 《Bioethics》2007,21(5):290-302