全文获取类型
收费全文 | 1079篇 |
免费 | 90篇 |
出版年
2022年 | 11篇 |
2021年 | 19篇 |
2019年 | 10篇 |
2018年 | 22篇 |
2017年 | 9篇 |
2016年 | 19篇 |
2015年 | 34篇 |
2014年 | 51篇 |
2013年 | 71篇 |
2012年 | 39篇 |
2011年 | 57篇 |
2010年 | 47篇 |
2009年 | 27篇 |
2008年 | 48篇 |
2007年 | 53篇 |
2006年 | 38篇 |
2005年 | 35篇 |
2004年 | 39篇 |
2003年 | 36篇 |
2002年 | 21篇 |
2001年 | 35篇 |
2000年 | 29篇 |
1999年 | 27篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 31篇 |
1991年 | 26篇 |
1990年 | 22篇 |
1989年 | 29篇 |
1988年 | 18篇 |
1987年 | 22篇 |
1986年 | 26篇 |
1985年 | 24篇 |
1984年 | 10篇 |
1981年 | 13篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 10篇 |
1976年 | 12篇 |
1975年 | 10篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1972年 | 8篇 |
1970年 | 7篇 |
1969年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有1169条查询结果,搜索用时 343 毫秒
71.
Wareed Ahmed Anuradha Gopal Bhat Majety Naga Leelaram Shruti Menon Valakunja Nagaraja 《Nucleic acids research》2013,41(15):7462-7471
Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn2+ finger motifs in the CTD. The Zn2+ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn2+ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn2+ fingers from the mycobacterial topoI could be associated with Zn2+ export and homeostasis. 相似文献
72.
Madeleine Scharf Stefan Neef Robert Freund Cornelia Geers-Kn?rr Mirita Franz-Wachtel Almuth Brandis Dorothee Krone Heike Schneider Stephanie Groos Manoj B. Menon Kin-Chow Chang Theresia Kraft Joachim D. Meissner Kenneth R. Boheler Lars S. Maier Matthias Gaestel Renate J. Scheibe 《Molecular and cellular biology》2013,33(13):2586-2602
73.
74.
75.
Daria?S. Khvostichenko Johnathan?J.D. Ng Sarah?L. Perry Monisha Menon Paul?J.A. Kenis 《Biophysical journal》2013,105(8):1848-1859
Using small-angle x-ray scattering (SAXS), we investigated the phase behavior of mesophases of monoolein (MO) mixed with additives commonly used for the crystallization of membrane proteins from lipidic mesophases. In particular, we examined the effect of sodium and potassium phosphate salts and the detergent β-octylglucoside (βOG) over a wide range of compositions relevant for the crystallization of membrane proteins in lipidic mesophases. We studied two types of systems: 1), ternary mixtures of MO with salt solutions above the hydration boundary; and 2), quaternary mixtures of MO with βOG and salt solutions over a wide range of hydration conditions. All quaternary mixtures showed highly regular lyotropic phase behavior with the same sequence of phases (Lα, Ia3d, and Pn3m) as MO/water mixtures at similar temperatures. The effects of additives in quaternary systems agreed qualitatively with those found in ternary mixtures in which only one additive is present. However, quantitative differences in the effects of additives on the lattice parameters of fully hydrated mesophases were found between ternary and quaternary mixtures. We discuss the implications of these findings for mechanistic investigations of membrane protein crystallization in lipidic mesophases and for studies of the suitability of precipitants for mesophase-based crystallization methods. 相似文献
76.
Hisham Mohammed Clive D’Santos Aurelien A. Serandour H. Raza Ali Gordon D. Brown Alan Atkins Oscar M. Rueda Kelly A. Holmes Vasiliki Theodorou Jessica L.L. Robinson Wilbert Zwart Amel Saadi Caryn S. Ross-Innes Suet-Feung Chin Suraj Menon John Stingl Carlo Palmieri Carlos Caldas Jason S. Carroll 《Cell reports》2013,3(2):342-349
- Download : Download full-size image
77.
78.
Mark Pennington Aleksandra Gentry-Maharaj Chloe Karpinskyj Alec Miners Julie Taylor Ranjit Manchanda Rema Iyer Michelle Griffin Andy Ryan Ian Jacobs Usha Menon Rosa Legood 《PloS one》2016,11(11)
BackgroundThere is limited evidence on the costs of Endometrial Cancer (EC) by stage of disease. We estimated the long-term secondary care costs of EC according to stage at diagnosis in an English population-based cohort.MethodsWomen participating in UKCTOCS and diagnosed with EC following enrolment (2001–2005) and prior to 31st Dec 2009 were identified to have EC through multiple sources. Survival was calculated through data linkage to death registry. Costs estimates were derived from hospital records accessed from Hospital Episode Statistics (HES) with additional patient level covariates derived from case notes and patient questionnaires. Missing and censored data was imputed using Multiple Imputation. Regression analysis of cost and survival was undertaken.Results491 of 641 women with EC were included. Five year total costs were strongly dependent on stage, ranging from £9,475 (diagnosis at stage IA/IB) to £26,080 (diagnosis at stage III). Stage, grade and BMI were the strongest predictors of costs. The majority of costs for stage I/II EC were incurred in the first six months after diagnosis while for stage III / IV considerable costs accrued after the first six months.ConclusionsIn addition to survival advantages, there are significant cost savings if patients with EC are detected earlier. 相似文献
79.
Phuong H. Nguyen Sunny S. Kim Tuan T. Nguyen Lan M. Tran Nemat Hajeebhoy Edward A. Frongillo Marie T. Ruel Rahul Rawat Purnima Menon 《PloS one》2016,11(3)
Adequate utilization of services is critical to maximize the impact of counselling on infant and young child feeding (IYCF), but little is known about factors affecting utilization. Our study examined supply- and demand-side factors associated with the utilization of IYCF counselling services in Viet Nam. We used survey data from mothers with children <2y (n = 1,008) and health staff (n = 60) from the evaluation of a program that embedded IYCF counseling into the existing government health system. The frequency of never users, one-time users, repeat users, and achievers of the recommended minimum number of visits at health facilities were 45.1%, 13.0%, 28.4% and 13.5%, respectively. Poisson regression showed that demand-generation strategies, especially invitation cards, were the key factors determining one-time use (Prevalence ratio, PR 3.0, 95% CI: 2.2–4.2), repeated use (PR 3.2, 95% CI: 2.4–4.2), and achievement of minimum visits (PR 5.5, 95% CI: 3.6–8.4). Higher maternal education was associated with higher utilization both for one-time and repeated use. Being a farmer, belonging to an ethnic minority, and having a wasted child were associated with greater likelihood of achieving the minimum recommended number of visits, whereas child stunting or illness were not. Distance to health center was a barrier to repeated visits. Among supply-side factors, good counselling skills (PR: 1.3–1.8) was the most important factor associated with any service use, whereas longer employment duration and greater work pressure of health center staff were associated with lower utilization. Population attributable risk estimations showed that an additional 25% of the population would have achieved the minimum number of visits if exposed to three demand-generation strategies, and further increased to 49% if the health staff had good counseling skills and low work pressure. Our study provides evidence that demand-generation strategies are essential to increase utilization of facility-based IYCF counselling services in Viet Nam, and may be relevant for increasing and sustaining use of nutrition services in similar contexts. 相似文献
80.
A. B. Shreya Renuka S. Managuli Jyothsna Menon Lavanya Kondapalli Aswathi R. Hegde Kiran Avadhani 《Journal of liposome research》2016,26(3):221-232
Context: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM.Objective: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches.Materials and methods: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration.Results and discussion: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0?nm, PDI of 0.232, ZP of??43.7?mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24?h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3?μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p?0.05) increase in bioavailability upon transdermal application compared with oral route.Conclusion: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM. 相似文献