全文获取类型
收费全文 | 448篇 |
免费 | 53篇 |
出版年
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 13篇 |
2014年 | 6篇 |
2013年 | 20篇 |
2012年 | 25篇 |
2011年 | 22篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 13篇 |
2007年 | 17篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 11篇 |
2003年 | 22篇 |
2002年 | 6篇 |
2001年 | 15篇 |
2000年 | 15篇 |
1999年 | 7篇 |
1998年 | 11篇 |
1997年 | 11篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1993年 | 5篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 14篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1967年 | 3篇 |
1932年 | 2篇 |
排序方式: 共有501条查询结果,搜索用时 218 毫秒
71.
In Rhodobacter sphaeroides, MreB, MreC, MreD, PBP2, and RodA are encoded at the same locus. The localizations of PBP2, MreB, and MreC, which have all been implicated in the synthesis of the peptidoglycan layer, were investigated under different growth conditions to gain insight into the relationships between these proteins. Immunofluorescence microscopy showed that PBP2 localized to specific sites at the midcell of elongating cells under both aerobic and photoheterotrophic conditions. Visualizing PBP2 at different stages of the cell cycle showed that in elongating cells, PBP2 was found predominately at the midcell, with asymmetric foci and bands across the cell. PBP2 remained at midcell until the start of septation, after which it moved to midcell of the daughter cells. Deconvolution and three-dimensional reconstructions suggested that PBP2 forms a partial ring at the midcell of newly divided cells and elongated cells, while in septating cells, partial PBP2 rings were present at one-quarter and three-quarter positions. Due to the diffraction limits of light microscopy, these partial rings could represent unresolved helices. Colocalization studies showed that MreC always colocalized with PBP2, while MreB colocalized with PBP2 only during elongation; during septation, MreB remained at the septation site, whereas PBP2 relocalized to the one-quarter and three-quarter positions. These results suggest that PBP2 and MreC are involved in peptidoglycan synthesis during elongation and that this occurs at specific sites close to midcell in R. sphaeroides. 相似文献
72.
Conroy DA Hairston IS Arnedt JT Hoffmann RF Armitage R Brower KJ 《Chronobiology international》2012,29(1):35-42
Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00-06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=?-2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats. 相似文献
73.
Brown MT Steel BC Silvestrin C Wilkinson DA Delalez NJ Lumb CN Obara B Armitage JP Berry RM 《Journal of bacteriology》2012,194(13):3495-3501
Swimming Escherichia coli cells are propelled by the rotary motion of their flagellar filaments. In the normal swimming pattern, filaments positioned randomly over the cell form a bundle at the posterior pole. It has long been assumed that the hook functions as a universal joint, transmitting rotation on the motor axis through up to ~90° to the filament in the bundle. Structural models of the hook have revealed how its flexibility is expected to arise from dynamic changes in the distance between monomers in the helical lattice. In particular, each of the 11 protofilaments that comprise the hook is predicted to cycle between short and long forms, corresponding to the inside and outside of the curved hook, once each revolution of the motor when the hook is acting as a universal joint. To test this, we genetically modified the hook so that it could be stiffened by binding streptavidin to biotinylated monomers, impeding their motion relative to each other. We found that impeding the action of the universal joint resulted in atypical swimming behavior as a consequence of disrupted bundle formation, in agreement with the universal joint model. 相似文献
74.
T. Ripperger B. Schlegelberger PD Dr. rer. nat. D. Steinemann 《Medizinische Genetik》2012,24(1):33-39
Juvenile myelomonocytic leukemia (JMML) is a unique myeloproliferative disorder of early childhood in which mutations in NRAS, KRAS, PTPN11, NF1 and CBL are frequently found. Using high-resolution oligo array-based comparative genomic hybridization (aCGH), 20 JMML samples were investigated for submicroscopic genomic copy number alterations. Besides known cytogenetic aberrations, ten samples displayed additional submicroscopic alterations. Interestingly, an almost identical gain of chromosome 8 was identified in two patients. Subsequently, fluorescence in situ hybridization indicated a constitutional partial trisomy 8 mosaic (cT8M) in both patients. A survey on 27 cT8M patients with reported malignancies showed a predominance of myeloid malignancies including JMML. Our results dramatically reduce the critical region on chromosome 8 to 8p11.21q11.21. To determine how constitutional partial trisomy 8 mosaicisms may contribute to leukemogenesis in different mutational subtypes of JMML and other myeloid malignancies, further investigations are required. 相似文献
75.
76.
PD Dr. Stefan Pelzer 《当今生物学》2012,42(2):98-106
Tailor‐made microorganisms Microbial diversity provides unlimited resources for the development of novel industrial processes and products. Since the beginning of the 20th century microorganisms have been successfully applied for the large scale production of bio‐based products. In recent years, modern methods of strain development and Synthetic Biology have enabled biotech engineers to design even more sophisticated and tailor‐made microorganisms. These microbes serve industrial processes for the production of bulk chemicals, enzymes, polymers, biofuels as well as plant‐derived ingredients such as Artemisinin in an ecologically and economically sustainable and attractive fashion. In the future, production of advanced biofuels, microbial fuel cells, CO2 as feedstock and microbial cellulose are research topics as well as challenges of global importance. Continuous efforts in microbiology and biotechnology research will be pivotal for white biotechnology to gain more momentum in transforming the chemical industry towards a knowledge based bio‐economy. 相似文献
77.
Abraham JE Maranian MJ Spiteri I Russell R Ingle S Luccarini C Earl HM Pharoah PD Dunning AM Caldas C 《BMC medical genomics》2012,5(1):19-6
ABSTRACT: BACKGROUND: The increasing trend for incorporation of biological sample collection within clinical trials requires sample collection procedures which are convenient and acceptable for both patients and clinicians. This study investigated the feasibility of using saliva-extracted DNA in comparison to blood-derived DNA, across two genotyping platforms: Applied Biosystems Taqman TM and Illumina Beadchip TM genome-wide arrays. METHOD: Patients were recruited from the Pharmacogenetics of Breast Cancer Chemotherapy (PGSNPS) study. Paired blood and saliva samples were collected from 79 study participants. The Oragene DNA Self-Collection kit (DNAgenotek(R)) was used to collect and extract DNA from saliva. DNA from EDTA blood samples (median volume 8 ml) was extracted by GenProbe, Livingstone, UK. DNA yields, standard measures of DNA quality, genotype call rates and genotype concordance between paired, duplicated samples were assessed. RESULTS: Total DNA yields were lower from saliva (mean 24 ug, range 0.2-52 ug) than from blood (mean 210 ug, range 58-577 ug) and a 2-fold difference remained after adjusting for the volume of biological material collected. Protein contamination and DNA fragmentation measures were greater in saliva DNA. 78/79 saliva samples yielded sufficient DNA for use on Illumina Beadchip arrays and using Taqman assays. Four samples were randomly selected for genotyping in duplicate on the Illumina Beadchip arrays. All samples were genotyped using Taqman assays. DNA quality, as assessed by genotype call rates and genotype concordance between matched pairs of DNA was high (>97%) for each measure in both blood and saliva-derived DNA. CONCLUSION: We conclude that DNA from saliva and blood samples is comparable when genotyping using either Taqman assays or genome-wide chip arrays. Saliva sampling has the potential to increase participant recruitment within clinical trials, as well as reducing the resources and organisation required for multicentre sample collection. 相似文献
78.
Henry SL Bensley JG Wood-Bradley RJ Cullen-McEwen LA Bertram JF Armitage JA 《The international journal of biochemistry & cell biology》2012,44(3):435-440
Globally 30% of adults are overweight or obese. The white adipocyte is a major component of adipose tissue, and as the obesity epidemic increases it is critically important to understand the factors determining adipocyte development and function. Adipogenesis has two distinct phases; determination of the adipocyte from a multipotent stem cell, and terminal differentiation of a pre-adipocyte into a mature adipocyte. The environment encountered in early life can alter adipocyte number and size and potentially impact upon adipocyte endocrine function in adulthood. These alterations may contribute to the pathophysiology of chronic diseases and thus targeted therapy of the adipocyte has great potential for treating the current obesity epidemic. 相似文献
79.
David T Pride Julia Salzman Matthew Haynes Forest Rohwer Clara Davis-Long Richard A White III Peter Loomer Gary C Armitage David A Relman 《The ISME journal》2012,6(5):915-926
Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host–virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity. 相似文献
80.
Overview of Mathematical Approaches Used to Model Bacterial Chemotaxis II: Bacterial Populations 总被引:1,自引:0,他引:1
We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The
application of continuum mathematical models, in particular generalized Keller–Segel models, is discussed along with attempts
to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species
of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter
values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial
populations. Various aspects of each model are discussed and areas for possible future research are postulated. 相似文献