全文获取类型
收费全文 | 321篇 |
免费 | 18篇 |
专业分类
339篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 22篇 |
2014年 | 18篇 |
2013年 | 17篇 |
2012年 | 33篇 |
2011年 | 24篇 |
2010年 | 23篇 |
2009年 | 17篇 |
2008年 | 14篇 |
2007年 | 22篇 |
2006年 | 13篇 |
2005年 | 14篇 |
2004年 | 15篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有339条查询结果,搜索用时 11 毫秒
151.
Om Prakash Yogesh Shouche Kamlesh Jangid Joel E. Kostka 《Applied microbiology and biotechnology》2013,97(1):51-62
Despite tremendous advances in microbial ecology over the past two decades, traditional cultivation methods have failed to grow ecologically more relevant microorganisms in the laboratory, leading to a predominance of weed-like species in the world’s culture collections. In this review, we highlight the gap between culture-based and culture-independent methods of microbial diversity analysis, especially in investigations of slow growers, oligotrophs, and fastidious and recalcitrant microorganisms. Furthermore, we emphasize the importance of microbial cultivation and the acquisition of the cultivation-based phenotypic data for the testing of hypotheses arising from genomics and proteomics approaches. Technical difficulties in cultivating novel microorganisms and how modern approaches have helped to overcome these limitations are highlighted. After cultivation, adequate preservation without changes in genotypic and phenotypic features of these microorganisms is necessary for future research and training. Hence, the contribution of microbial resource centers in the handling, preservation, and distribution of this novel diversity is discussed. Finally, we explore the concept of microbial patenting and requisite guidelines of the “Budapest Treaty” for establishment of an International Depositary Authority. 相似文献
152.
Shyam Sundar Sharma Madan Singh Negi Pratima Sinha Kamlesh Kumar Shashi Bhushan Tripathi 《Plant Molecular Biology Reporter》2011,29(1):12-18
Efficacy of two dominant molecular markers, namely, amplified fragment length polymorphism (AFLP) and three endonuclease (TE)-AFLP,
were assessed in 20 individuals of the biodiesel species Pongamia pinnata. Four primer combinations generated a total of 254 and 194 bands in AFLP and TE-AFLP, respectively. Both techniques could
unequivocally identify each accession used in this study. The Jaccard’s similarity coefficient ranged from 0.30 to 0.90 for
AFLP and from 0.25 to 0.85 for TE-AFLP. The correlation coefficient between AFLP and TE-AFLP dendrogram was 0.56 which was
low but significant (P < 0.001). Values of effective multiplex ratio, marker index, and resolving power were markedly higher in AFLP than in TE-AFLP.
However, the band intensities across different lanes were uniform in TE-AFLP leading to easy and accurate scoring of gels
which resulted in slightly higher bootstrap values with TE-AFLP data as compared to AFLP data. Inferences based on TE-AFLP
data had similar level of biological relevance as compared to AFLP data when location and diameter of trees were taken in
to consideration. However, the easy scorability of TE-AFLP profiles is extremely important and especially desirable in studies
requiring genotyping of large number of individuals distributed across many gels. 相似文献
153.
Madhusudan K. Vasudevamurthy Laurence R. Weatherley Michael Lever 《Biocatalysis and Biotransformation》2005,23(3):285-291
The protective effect of the synthetic compensatory solutes, dimethylthetin (CAS 4727-41-7) and homodeanol betaine (N, N-dimethyl-N-(2-hydroxyethyl)-N-(2 carboxyethyl) ammonium inner salt, CAS 6249-53-2), on two enzymes: lactate dehydrogenase (LDH from rabbit muscle) and a microbial lipase, was compared with that of glycine betaine, trehalose and sorbitol. When the enzyme plus 1 M solute were heated for 10 min at temperatures between 35-75°C, the temperature at which 50% of enzyme activity was lost increased most in the presence of trehalose (7.9° for LDH, 11.6° for lipase) and homodeanol betaine (10.7° for LDH, 11.0° for lipase). With both enzymes, more activity was retained at extreme temperatures in the presence of homodeanol betaine than with trehalose. Glycine betaine, dimethylthetin and sorbitol were less effective. Enzyme plus 1 M stabilizer solutions were frozen at -30°C and freeze-dried for 24 h. Trehalose was the most effective stabilizer of lactate dehydrogenase, and homodeanol betaine of lipase, during freeze-drying. 相似文献
154.
Kamlesh Madhusudan Makwana Radhakrishnan Mahalakshmi 《Protein science : a publication of the Protein Society》2015,24(12):1920-1933
With increasing structural information on proteins, the opportunity to understand physical forces governing protein folding is also expanding. One of the significant non‐covalent forces between the protein side chains is aromatic–aromatic interactions. Aromatic interactions have been widely exploited and thoroughly investigated in the context of folding, stability, molecular recognition, and self‐assembly processes. Through this review, we discuss the contribution of aromatic interactions to the activity and stability of thermophilic, mesophilic, and psychrophilic proteins. Being hydrophobic, aromatic amino acids tend to reside in the protein hydrophobic interior or transmembrane segments of proteins. In such positions, it can play a diverse role in soluble and membrane proteins, and in α‐helix and β‐sheet stabilization. We also highlight here some excellent investigations made using peptide models and several approaches involving aryl–aryl interactions, as an increasingly popular strategy in protein and peptide engineering. A recent survey described the existence of aromatic clusters (trimer, tetramer, pentamer, and higher order assemblies), revealing the self‐associating property of aryl groups, even in folded protein structures. The application of this self‐assembly of aromatics in the generation of modern bionanomaterials is also discussed. 相似文献
155.
Epco Hasker Paritosh Malaviya Kamlesh Gidwani Albert Picado Bart Ostyn Sangeeta Kansal Rudra Pratap Singh Om Prakash Singh Ankita Chourasia Abhishek Kumar Singh Ravi Shankar Mary E. Wilson Basudha Khanal Suman Rijal Marleen Boelaert Shyam Sundar 《PLoS neglected tropical diseases》2014,8(1)
Introduction
Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4–10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers.Methods
We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified.Results
We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers.Discussion
There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies. 相似文献156.
Gidwani K Picado A Rijal S Singh SP Roy L Volfova V Andersen EW Uranw S Ostyn B Sudarshan M Chakravarty J Volf P Sundar S Boelaert M Rogers ME 《PLoS neglected tropical diseases》2011,5(9):e1296
Background
Visceral leishmaniasis is the world'' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial.Methods
As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention.Results
A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi.Conclusions
This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions. 相似文献157.
B-Rao C Kulkarni-Almeida A Katkar KV Khanna S Ghosh U Keche A Shah P Srivastava A Korde V Nemmani KV Deshmukh NJ Dixit A Brahma MK Bahirat U Doshi L Sharma R Sivaramakrishnan H 《Bioorganic & medicinal chemistry》2012,20(9):2930-2939
In recent years, xanthine oxidase has emerged as an important target not only for gout but also for cardiovascular and metabolic disorders involving hyperuricemia. Contrary to popular belief, recent clinical trials with uricosurics have demonstrated that enhanced excretion of uric acid is, by itself, not adequate to treat hyperuricemia; simultaneous inhibition of production of uric acid by inhibition of xanthine oxidase is also important. Virtual screening of in-house synthetic library followed by in vitro and in vivo testing led to the identification of a novel scaffold for xanthine oxidase inhibition. In vitro activity results corroborated the results from molecular docking studies of the virtual screening hits. The isocytosine scaffold maintains key hydrogen bonding and pi-stacking interactions in the deep end of the xanthine-binding pocket, which anchors it in an appropriate pose to inhibit binding of xanthine and shows promise for further lead optimization using structure-based drug design approach. 相似文献
158.
159.
Jacob J. Michaelson Yujian Shi Madhusudan Gujral Hancheng Zheng Dheeraj Malhotra Xin Jin Minghan Jian Guangming Liu Douglas Greer Abhishek Bhandari Wenting Wu Roser Corominas Áine Peoples Amnon Koren Athurva Gore Shuli Kang Guan Ning Lin Jasper Estabillo Therese Gadomski Balvindar Singh Kun Zhang Natacha Akshoomoff Christina Corsello Steven McCarroll Lilia M. Iakoucheva Yingrui Li Jun Wang Jonathan Sebat 《Cell》2012
160.
N Armstrong D Baines R Baker R Crossman M Davies A Hardy K Khunti S Kumar JP O Hare NT Raymond P Saravanan N Stallard A Szczepura A Wilson 《Trials》2012,13(1):164
ABSTRACT: BACKGROUND: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. METHODS: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control).Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice.orControl group: Standard GP care, with referral to secondary care as required, but no access to ICCD.Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (<=7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients. DISCUSSION: Forty-nine practices have been randomized, 1,997 patients have been recruited to the trial, and 20 patients have been recruited to the qualitative study. Results will be available late 2012.Trial registration[ClinicalTrials.gov: Identifier NCT00945204]. 相似文献