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11.
Leila Malik Jesper Nygaard Niels J. Christensen Werner W. Streicher Peter W. Thulstrup Lise Arleth Knud J. Jensen 《Journal of peptide science》2013,19(5):283-292
α‐Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix‐containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small‐angle X‐ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self‐assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self‐assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
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Managing and controlling wildlife species within Europe is an acknowledged part of conservation management, yet deciding and setting a population target in order to control a population is perceived to be conceptually very challenging. We interviewed stakeholders, within a variety of governmental and non-governmental organizations, to evaluate their perspectives about setting population targets as part of waterbird management for controlling population sizes. We conclude that the setting of a quantifiable population target is beneficial as a measurable objective for monitoring and evaluating management actions. However, it must be recognised as just one possible measurable objective and there may well be multiple supporting objectives that encapsulate the management aims of different stakeholders. When considering wide-scale control of waterbirds species, where it is likely that population size matters, any population target should be coupled to the issues being addressed. We highlight that it is important to actively engage with stakeholders as part of the decision-making process, not only to gain consensus but to share knowledge. A clear understanding of the context and the rationale for controlling a waterbird species is needed to align the interests of diverse stakeholders. The provision of scientific data and the continuous monitoring of management actions is viewed as beneficial and demanded by stakeholders, as part of any decision-making process when setting population targets. This facilitates effective evaluation of management actions, helping managers make wise decisions as well as enabling the continued development of management plans. 相似文献
14.
Brian Lohse Charlotte Helgstrand Jan B. L. Kristensen Ulrike Leurs Paul A. C. Cloos Jesper L. Kristensen Rasmus P. Clausen 《PloS one》2013,8(7)
Posttranslational modifications (PTMs) of the histone H3 tail such as methylation, acetylation and phosphorylation play important roles in epigenetic signaling. Here we study the effect of some of these PTMs on the demethylation rates of methylated lysine 9 in vitro using peptide substrates mimicking histone H3. Various combinations with other PTMs were employed to study possible cross-talk effects by comparing enzyme kinetic characteristics. We compared the kinetics of histone tail substrates for truncated histone lysine demethylases KDM4A and KDM4C containing only the catalytic core (cc) and some combinations were characterized on full length (FL) KDM4A and KDM4C. We found that the substrates combining trimethylated K4 and K9 resulted in a significant increase in the catalytic activity for FL-KDM4A. For the truncated versions of KDM4A and KDM4C a two-fold increase in the catalytic activity toward bis-trimethylated substrates could be observed. Furthermore, a significant difference in the catalytic activity between dimethylated and trimethylated substrates was found for full length demethylases in line with what has been reported previously for truncated demethylases. Histone peptide substrates phosphorylated at T11 could not be demethylated by neither truncated nor full length KDM4A and KDM4C, suggesting that phosphorylation of threonine 11 prevents demethylation of the H3K9me3 mark on the same peptide. Acetylation of K14 was also found to influence demethylation rates significantly. Thus, for truncated KDM4A, acetylation on K14 of the substrate leads to an increase in enzymatic catalytic efficiency (k
cat/K
m), while for truncated KDM4C it induces a decrease, primarily caused by changes in K
m. This study demonstrates that demethylation activities towards trimethylated H3K9 are significantly influenced by other PTMs on the same peptide, and emphasizes the importance of studying these interactions at the peptide level to get a more detailed understanding of the dynamics of epigenetic marks. 相似文献
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Pedro M. D. Moreno Sylvain Geny Y. Vladimir Pabon Helen Bergquist Eman M. Zaghloul Cristina S. J. Rocha Iulian I. Oprea Burcu Bestas Samir EL Andaloussi Per T. J?rgensen Erik B. Pedersen Karin E. Lundin Rula Zain Jesper Wengel C. I. Edvard Smith 《Nucleic acids research》2013,41(5):3257-3273
In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasion into duplex DNA (DSI). We thus report on the development of a clamp type of LNA ON—bisLNA—with capacity to bind and invade into supercoiled double-stranded DNA. The bisLNA links a triplex-forming, Hoogsteen-binding, targeting arm with a strand-invading Watson–Crick binding arm. Optimization was carried out by varying the number and location of LNA nucleotides and the length of the triplex-forming versus strand-invading arms. Single-strand regions in target duplex DNA were mapped using chemical probing. By combining design and increase in LNA content, it was possible to achieve a 100-fold increase in potency with 30% DSI at 450 nM using a bisLNA to plasmid ratio of only 21:1. Although this first conceptual report does not address the utility of bisLNA for the targeting of DNA in a chromosomal context, it shows bisLNA as a promising candidate for interfering also with cellular genes. 相似文献
17.
Arctic plants and herbivores are subject to ongoing climatic changes that are more rapid and extreme than elsewhere on the planet, and thus it is pivotal to understand the arctic plant-herbivore interactions in a global change context. We examined how infestation by an eriophyoid gall mite affects the circumpolar shrub Salix arctica, and how the effects vary across vegetation types. Specifically, we compared multiple leaf characteristics (leaf area, biomass, nutrient levels, δ15N and δ13C, and stress and performance of the photosynthetic apparatus) of infested leaves to those of un-infested leaves. Furthermore, we examined how altered environmental conditions, here experimentally manipulated levels of temperature, water and nutrients, shading, and UV-B radiation, affect the prevalence, density, and intensity of gall mite infestation and its impacts on S. arctica. Infested leaves were smaller in area and biomass and had lower nitrogen and carbon pools. However, their carbon concentration was higher, possibly because the galls acted as carbon sinks. The smaller photosynthetic area and lower nutrient content caused increased stress on the photosynthetic apparatus in infested leaves. The remaining leaf tissue responded with a higher photosynthetic performance, although there were indications of a general reduction in photosynthesis. Female leaves were more affected than male leaves. The experimental manipulations of environmental conditions did not affect the gall prevalence, density, or intensity on S. arctica leaves. Rather, plants responded positively to the treatments, reducing the effects of the galls to in-significance. This suggests a higher tolerance and defense against gall mites under future climate conditions. 相似文献
18.
Sarah Preisler Matejka Rebolj Anette Untermann Ditte M?ller Ejegod Elsebeth Lynge Carsten Rygaard Jesper Bonde 《PloS one》2013,8(3)
New commercially available Human Papillomavirus (HPV) assays need to be evaluated in a variety of cervical screening settings. Cobas HPV Test (cobas) is a real-time PCR-based assay allowing for separate detection of HPV genotypes 16 and 18 and a bulk of 12 other high-risk genotypes. The aim of the present study, Horizon, was to assess the prevalence of high-risk HPV infections in an area with a high background risk of cervical cancer, where women aged 23–65 years are targeted for cervical screening. We collected 6,258 consecutive cervical samples from the largest cervical screening laboratory in Denmark serving the whole of Copenhagen. All samples were stored in SurePath media. In total, 5,072 samples were tested with cobas, Hybrid Capture 2 High Risk HPV DNA test (HC2) and liquid-based cytology. Of these, 27% tested positive on cobas. This proportion decreased by age, being 43% in women aged 23–29 years and 10% in women aged 60–65 years. HC2 assay was positive in 20% of samples, and cytology was abnormal (≥ atypical squamous cells of undetermined significance) for 7% samples. When only samples without recent abnormalities were taken into account, 24% tested positive on cobas, 19% on HC2, and 5% had abnormal cytology. The proportion of positive cobas samples was higher than in the ATHENA trial. The age-standardized cobas positivity vs. cytology abnormality was 3.9 in our study and 1.7 in ATHENA. If in Copenhagen the presently used cytology would be replaced by cobas in women above age 30 years, an extra 11% of women would based on historical data be expected to have a positive cobas test without an underlying cervical intraepithelial lesion grade 3 or worse. Countries with a high prevalence of HPV infections should therefore proceed to primary HPV-based cervical screening with caution. 相似文献
19.
The present paper examines the relation between size, accumulation and performance for research grants, where we examine the relation between grant size for Centres of Excellence (CoE) funded by the Danish National Research Foundation (DNRF) and various ex post research performance measures, including impact and shares of highly cited articles. We examine both the relation between size and performance and also how performance for CoEs evolves over the course of grant periods. In terms of dynamics, it appears that performance over the grant period (i.e. 10 years) is falling for the largest CoEs, while it is increasing for those among the smallest half. Overall, multivariate econometric analysis finds evidence that performance is increasing in grant size and over time. In both cases, the relation appears to be non-linear, suggesting that there is a point at which performance peaks. The CoEs have also been very successful in securing additional funding, which can be viewed as a ‘cumulative effect’ of center grants. In terms of new personnel, the far majority of additional funding is spent on early career researchers, hence, this accumulation would appear to have a ‘generational’ dimension, allowing for scientific expertise to be passed on to an increasing number of younger researchers. 相似文献
20.
Christiane Elisabeth S?rensen Katerina Tritsaris Jesper Reibel Martin Lauritzen Erik Lykke Mortensen Merete Osler Anne Marie Lynge Pedersen 《PloS one》2016,11(3)