全文获取类型
收费全文 | 266篇 |
免费 | 23篇 |
专业分类
289篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 13篇 |
2015年 | 20篇 |
2014年 | 23篇 |
2013年 | 14篇 |
2012年 | 19篇 |
2011年 | 16篇 |
2010年 | 13篇 |
2009年 | 7篇 |
2008年 | 7篇 |
2007年 | 16篇 |
2006年 | 10篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 13篇 |
2002年 | 10篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有289条查询结果,搜索用时 15 毫秒
131.
Chagas CM Honorato TL Pinto GA Maia GA Rodrigues S 《Bioprocess and biosystems engineering》2007,30(3):207-215
Cashew apples are considered agriculture excess in the Brazilian Northeast because cashew trees are cultivated primarily with
the aim of cashew nut production. In this work, the use of cashew apple juice as a substrate for Leuconostoc mesenteroides cultivation was investigated. The effect of yeast extract and phosphate addition was evaluated using factorial planning tools.
Both phosphate and yeast extract addition were significant factors for biomass growth, but had no significant effect on maximum
enzyme activity. The enzyme activities found in cashew apple juice assays were at least 3.5 times higher than the activity
found in the synthetic medium. Assays with pH control (pH = 6.5) were also carried out. The pH-controlled fermentation enhanced
biomass growth, but decreased the enzyme activity. Crude enzyme free of cells produced using cashew apple juice was stable
for 16 h at 30°C at a pH of 5.0. 相似文献
132.
Natália H Mendes Fernando AF Melo Adolfo CB Santos José RC Pandolfi Elisabete A Almeida Rosilene F Cardoso Henri Berghs Suzana David Faber K Johansen Lívia G Espanha Sergio RA Leite Clarice QF Leite 《BMC research notes》2011,4(1):269
Background
Tuberculosis is a major health problem in São Paulo, Brazil, which is the most populous and one of the most cosmopolitan cities in South America. To characterize the genetic diversity of Mycobacterium tuberculosis in the population of this city, the genotyping techniques of spoligotyping and MIRU were applied to 93 isolates collected in two consecutive years from 93 different tuberculosis patients residing in São Paulo city and attending the Clemente Ferreira Institute (the reference clinic for the treatment of tuberculosis).Findings
Spoligotyping generated 53 different spoligotype patterns. Fifty-one isolates (54.8%) were grouped into 13 spoligotyping clusters. Seventy- two strains (77.4%) showed spoligotypes described in the international databases (SpolDB4, SITVIT), and 21 (22.6%) showed unidentified patterns. The most frequent spoligotype families were Latin American Mediterranean (LAM) (26 isolates), followed by the T family (24 isolates) and Haarlem (H) (11 isolates), which together accounted for 65.4% of all the isolates. These three families represent the major genotypes found in Africa, Central America, South America and Europe. Six Spoligo-International-types (designated SITs by the database) comprised 51.8% (37/72) of all the identified spoligotypes (SIT53, SIT50, SIT42, SIT60, SIT17 and SIT1). Other SITs found in this study indicated the great genetic diversity of M. tuberculosis, reflecting the remarkable ethnic diversity of São Paulo city inhabitants. The MIRU technique was more discriminatory and did not identify any genetic clusters with 100% similarity among the 93 isolates. The allelic analysis showed that MIRU loci 26, 40, 23 and 10 were the most discriminatory. When MIRU and spoligotyping techniques were combined, all isolates grouped in the 13 spoligotyping clusters were separated.Conclusions
Our data indicated the genomic stability of over 50% of spoligotypes identified in São Paulo and the great genetic diversity of M. tuberculosis isolates in the remaining SITs, reflecting the large ethnic mix of the São Paulo city inhabitants. The results also indicated that in this city, M. tuberculosis isolates acquired drug resistance independently of genotype and that resistance was more dependent on the selective pressure of treatment failure and the environmental circumstances of patients.133.
134.
Veronica Obregon-Perko Katherine M. Bricker Gloria Mensah Ferzan Uddin Mithra R. Kumar Emily J. Fray Robert F. Siliciano Nils Schoof Anna Horner Maud Mavigner Shan Liang Thomas Vanderford Julian Sass Cliburn Chan Stella J. Berendam Katharine J. Bar George M. Shaw Guido Silvestri Genevieve G. Fouda Sallie R. Permar Ann Chahroudi 《Journal of virology》2021,95(2)
135.
SVlm21 is a mutant of Sindbis virus which was isolated by serial passage of virus in mosquito cells maintained in low-methionine medium; it therefore has a low-methionine-resistant (LMR) phenotype. This phenotype requires mutations at nts 319 and 321; these mutations result in Arg to Leu and Ser to Cys changes at positions 87 and 88 respectively in the viral methyl transferase, nsP1. To better understand the genesis of SVlm21, we carried out serial passages of viruses having only one of these amino acid changes, but in mosquito cells maintained in normal methionine-medium. Whether the passage was begun with SV319 or with SV321, the dominant virus population which emerged always acquired the second SVlm21 amino acid change. However, when the passage was begun with virus having neither the nt 319 or the nt321 mutation, even after many passages neither of these mutations was seen in the passaged virus population. Virus with the LMR phenotype emerged earlier when the virus encoded a wild-type RDRP (passage 4) rather than the mutant RDRP encoded by SVpzf (passage 7). When the methionine concentration in the medium of mosquito cells was increased to 250 µM, more than 20 passages were required until the LMR phenotype predominated. Competition experiments were carried out to compare the relative fitness of SVlm21, SVwt, SV319 and SV321 to each other. Our results indicated that SVlm21 was dominant to SVwt, as well as to both SV319 and SV321. However, SV319 and SV321 were able to co-exist with SVwt implying that in these mixed infection the presence of SVwt inhibited the emergence of SVlm21. Finally, our experiments highlight how a virus population by mutation and selection can adapt to the intracellular concentration of a simple metabolite, S-adenosylmethionine. 相似文献
136.
Sabadin CS Benvegnú SA da Fontoura MM Saggin LM Tomimori J Fischman O 《Mycopathologia》2011,171(3):183-189
Onychomycosis and tinea pedis are common superficial infections caused primarily by dermatophytes. The aim of this investigation was to study the epidemiology,
etiological agents, and potential risk factors for infection based on comparison of athletes and non-athletes from a northern
region of Rio Grande do Sul (Brazil). Each group consisted of 100 male individuals with ages ranging from 18 to 40 years.
After a clinical examination, samples were taken from individuals presenting signs of onychomycosis and/or tinea pedis for direct microscopic examination and culture. Among the athletes, the frequency of onychomycosis and/or tinea pedis was 32%, and for the control group, it was 20%. The athletes presented 16% of onychomycosis, 12% of tinea pedis, and 4% of onychomycosis and tinea pedis together. The distribution in the control group was 10% of onychomycosis, 7% of tinea pedis, and 3% of this association. The pathogens identified were dermatophytes (84.8%) and yeasts (15.2%), and the most commonly
identified organism was Trichophyton rubrum, followed by Trichophyton mentagrophytes var. interdigitale. No significant differences were found when the frequency of species distribution in the athletes and non-athlete groups was
compared. Risk factors for onychomycosis in athletes included familial cases of fungal infection, contact with domestic animals,
and nail trauma, while the risk factors in non-athletes included the habit of not using sandals in public bathrooms and nail
trauma. For tinea pedis, the habit of not using sandals in public bathrooms was a predisposing factor in both groups, while hyperhydrosis was a risk
factor only in non-athletes. This study concludes that despite the higher number of fungal infections in athletes, there is
no significant difference between these groups. 相似文献
137.
Carl W. Decker Jerome Garcia Kristelle Gatchalian Deronisha Arceneaux Clarice Choi Si Cave Derick Han Jeniffer B. Hernandez 《Biochemistry and Biophysics Reports》2020
Mitochondria oscillate along a morphological continuum from fragmented individual units to hyperfused tubular networks. Their position at the junction of catabolic and anabolic metabolism couples this morphological plasticity, called mitochondrial dynamics, to larger cellular metabolic programs, which in turn implicate mitochondria in a number of disease states. In many cancers, fragmented mitochondria engage the cell with the biosynthetic capacity of aerobic glycolysis in service of proliferation and progression. Chemo-resistant cancers, however, favor remodeling dynamics that yield fused mitochondrial assemblies utilizing oxidative phosphorylation (OXPHOS) through the electron transport chain (ETC). In this study, expression of Mitofusin-2 (MFN-2), a GTPase protein mediator of mitochondrial fusion, was found to closely correlate to Jurkat leukemia cell survival post doxorubicin (DxR) assault. Moreover, this was accompanied by dramatically increased expression of OXPHOS respiratory complexes and ATP Synthase, as well as a commensurate escalation of state III respiration and respiratory control ratio (RCR). Importantly, CRISPR knockout of MFN-2 resulted in a considerable decrease of doxorubicin (DxR) median lethal dose compared to a treated wildtype control, suggesting an important role of mitochondrial fusion in chemotherapy sensitivity and acute resistance. 相似文献
138.
The chemo enzymatic functionalization of chitosan zeolite particles provides antioxidant and antimicrobial properties 下载免费PDF全文
Gregor Tegl Viktoria Stagl Anna Mensah Daniela Huber Walter Somitsch Stefanie Grosse‐Kracht Georg M. Guebitz 《Engineering in Life Science》2018,18(5):334-340
Silicate‐based microporous materials like zeolites are nano enabled particles and used for various applications including pharmaceutical formulations. This study reports on the chemo‐enzymatic functionalization of chitosan‐zeolite particles (CTS‐zeolites) with caffeic acid (CA) and glucose oxidase (GOX) to impart combined antioxidant and antimicrobial properties. CA was grafted on the chitosan moieties by using laccase generating stable particles (zeta potential –36.7 mV) of high antioxidant activity (44% DPPH inhibition). GOX was immobilized both on CTS‐zeolites and on CA modified CTS‐zeolites and creating a hydrogen peroxide generation system continuously and in‐situ producing this oxidative and antimicrobial agent. The system prevented bacterial growth of E. coli and S. aureus over 24 h whereby a steady‐state concentration of around 60 μM hydrogen peroxide in the culture medium was observed. CA and GOX functionalized CTS‐zeolite particles additionally showed combinatorial antioxidant and antimicrobial properties providing a powerful bioactive system for medical applications. These particles proved their suitability for incorporation in bioactive formulations which could be used, inter alia, for topical wound treatments. 相似文献
139.
Kofi A. Mensah Christopher T. Ritchlin Edward M. Schwarz 《Journal of cellular physiology》2010,223(1):76-83
Osteoclasts (OC) are multinucleated bone resorbing cells that form via RANKL‐induced fusion of heterogeneous mononuclear OC precursors (OCP). Currently, there are no unique surface markers to distinguish these OCP populations, which are diagnostic for erosive and metabolic bone diseases using culture assays. Thus, we investigated expression of DC‐STAMP, a surface receptor required for OCP fusion, during osteoclastogenesis in vitro using a novel monoclonal antibody (1A2). Immunoprecipitation‐Western blot analysis of OCP membrane proteins detected 106 kDa dimeric and 53 kDa monomeric DC‐STAMP in non‐denaturing and denaturing conditions, respectively, with greater sensitivity versus rabbit anti‐sera (KR104). 1A2 also detected 99.9% of undifferentiated monocytes as a single population by flow cytometry with a MFI 100‐fold over background, while KR104 was not useful in this assay. Functionally, 1A2 inhibited OCP fusion in vitro. RANKL stimulation of OCP induced DC‐STAMPlo and DC‐STAMPhi cells, which mature into OC and mononuclear cells respectively as determined by fluorescent microscopy and TRAP assays. Addition of DC‐STAMPhi cells to purified DC‐STAMPlo cultures produced larger, more nucleated OC vs. pure DC‐STAMPlo cultures. RT‐qPCR analysis of these two populations showed that OC markers (Trap and Oc‐stamp) and fusogenic gene expression (Cd9 and Cd47), were significantly increased in DC‐STAMPlo vs. DC‐STAMPhi cells. Collectively, these results demonstrate that DC‐STAMP is expressed on OCP as a dimer, which is efficiently detected by 1A2 via flow cytometry. RANKL induces osteoclastogenesis by stimulating DC‐STAMP internalization in some OCP, and these DC‐STAMPlo cells display the “master fusogen” phenotype. In contrast, DC‐STAMPhi OCP can only act as mononuclear donors. J. Cell. Physiol. 223: 76–83, 2010. © 2009 Wiley‐Liss, Inc. 相似文献