全文获取类型
收费全文 | 550篇 |
免费 | 54篇 |
出版年
2023年 | 6篇 |
2022年 | 5篇 |
2021年 | 12篇 |
2020年 | 8篇 |
2019年 | 17篇 |
2018年 | 16篇 |
2017年 | 14篇 |
2016年 | 20篇 |
2015年 | 30篇 |
2014年 | 44篇 |
2013年 | 32篇 |
2012年 | 48篇 |
2011年 | 35篇 |
2010年 | 31篇 |
2009年 | 19篇 |
2008年 | 28篇 |
2007年 | 41篇 |
2006年 | 26篇 |
2005年 | 21篇 |
2004年 | 33篇 |
2003年 | 27篇 |
2002年 | 25篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1977年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有604条查询结果,搜索用时 31 毫秒
1.
Agricultural biotechnologies embrace a large array of conventional and modern technologies, spanning from composting organic by-products of agriculture to innovative improvement of quality traits of about twenty out of the mostly cultivated plants. In EU a rather restrictive legislative framework has been installed for GMOs, requiring a risk assessment disproportionate with respect to conventional agriculture and organic farming products. The latter are far from being proved safe for human and animal health, and for the environment.Biotechnology of GMOs has been overtaken by biopolitics. On one side there are biotechnological challenges to be tackled, on another side there is plenty of ground for biopolitical decisions about GMOs. Perhaps the era of harsh confrontation could be fruitfully replaced by sensible cooperation, in order to get a sustainable agricultural development. 相似文献
2.
Identification and functional analysis of two U3 binding sites on yeast pre-ribosomal RNA. 总被引:51,自引:9,他引:42
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
It has long been known that U3 can be isolated hydrogen bonded to pre-ribosomal RNAs, but the sites of interaction are poorly characterized. Here we show that yeast U3 can be cross-linked to 35S pre-rRNA both in deproteinized extracts and in living cells. The sites of cross-linking were localized to the 5' external transcribed spacer (ETS) and then identified at the nucleotide level. Two regions of U3 near the 5' end are cross-linked to pre-rRNA in vivo and in vitro; the evolutionarily conserved box A region and a 10 nucleotide (nt) sequence with perfect complementarity to an ETS sequence. Two in vivo cross-links are detected in the ETS, at +470, within the region complementary to U3, and at +655, close to the cleavage site at the 5' end of 18S rRNA. A tagged rDNA construct was used to follow the effects of mutations in the ETS in vivo. A small deletion around the +470 cross-linking site in the ETS prevents the synthesis of 18S rRNA. This region is homologous to the site of vertebrate ETS cleavage. We propose that this site may be evolutionarily conserved to direct the assembly of a pre-rRNA processing complex required for the cleavages that generate 18S rRNA. 相似文献
3.
Mutational analysis of an essential binding site for the U3 snoRNA in the 5' external transcribed spacer of yeast pre-rRNA. 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The small nucleolar RNA U3 is essential for viability in yeast. We have previously shown that U3 can be cross-linked in vivo to the pre-rRNA in the 5' external transcribed spacer (ETS), at +470. This ETS region contains 10 nucleotides of perfect complementarity to U3. In a genetic background where the mutated rDNA is the only transcribed rDNA repeat, the deletion of the 10 nt complementary to U3 is lethal. Cells lacking the U3 complementary sequence in pre-rRNA fail to accumulate 18S rRNA: pre-rRNA processing is inhibited at sites A0 in the 5' ETS, A1 at the 5' end of 18S rRNA and A2 in ITS1. We show here that effects on processing at site A0 are specific for U3 and its associated proteins and are not seen on depletion of other snoRNP components. The deletion of the sequence complementary to U3 in the ETS therefore mimics all the known effects of the depletion of U3 in trans. This indicates that we have identified an essential U3 binding site on pre-rRNA, required in cis for the maturation of 18S rRNA. 相似文献
4.
Luigi Bosco Cristiana Valle Daniela Willems 《Development, growth & differentiation》1993,35(3):257-270
After lentectomy of larval Xenopus laevis , the outer cornea undergoes tissue transformation resulting in formation of a new lens. This lens regeneration is triggered and sustained by neural retina. In the present study, lens-forming transformation of the outer cornea was completed in vitro when the outer cornea was cultured within the lentectomized eye-cup. Well-differentiated lens fiber cells, which showed positive immunofluorescence for total crystallins, were also formed when the outer cornea was cultivated with the retina. No lens tissue was formed when the cornea was cultured alone. Lens-forming transformation, originating from the cornea three and five days after lentectomy, completely regressed when the tissue was isolated in vitro . Fom the present and previous findings, we concluded that, the interaction of corneal cells with the retina plays a decisive role in lens regeneration in situ . 相似文献
5.
Valentina Sora Adrian Otamendi Laspiur Kristine Degn Matteo Arnaudi Mattia Utichi Ludovica Beltrame Dayana De Menezes Matteo Orlandi Ulrik Kristoffer Stoltze Olga Rigina Peter Wad Sackett Karin Wadt Kjeld Schmiegelow Matteo Tiberti Elena Papaleo 《Protein science : a publication of the Protein Society》2023,32(1):e4527
Reliable prediction of free energy changes upon amino acid substitutions (ΔΔGs) is crucial to investigate their impact on protein stability and protein–protein interaction. Advances in experimental mutational scans allow high-throughput studies thanks to multiplex techniques. On the other hand, genomics initiatives provide a large amount of data on disease-related variants that can benefit from analyses with structure-based methods. Therefore, the computational field should keep the same pace and provide new tools for fast and accurate high-throughput ΔΔG calculations. In this context, the Rosetta modeling suite implements effective approaches to predict folding/unfolding ΔΔGs in a protein monomer upon amino acid substitutions and calculate the changes in binding free energy in protein complexes. However, their application can be challenging to users without extensive experience with Rosetta. Furthermore, Rosetta protocols for ΔΔG prediction are designed considering one variant at a time, making the setup of high-throughput screenings cumbersome. For these reasons, we devised RosettaDDGPrediction, a customizable Python wrapper designed to run free energy calculations on a set of amino acid substitutions using Rosetta protocols with little intervention from the user. Moreover, RosettaDDGPrediction assists with checking completed runs and aggregates raw data for multiple variants, as well as generates publication-ready graphics. We showed the potential of the tool in four case studies, including variants of uncertain significance in childhood cancer, proteins with known experimental unfolding ΔΔGs values, interactions between target proteins and disordered motifs, and phosphomimetics. RosettaDDGPrediction is available, free of charge and under GNU General Public License v3.0, at https://github.com/ELELAB/RosettaDDGPrediction . 相似文献
6.
Cristiana Sbrana Manuela Giovannetti Marcello Buiatti Emanuela Storti 《Journal of Phytopathology》1993,139(1):1-9
Tissue cultures of Nicotiana tabacum were utilized to investigate the mechanisms associated with host specificity and non-host incompatibility in mycorrhizal and pathogenic fungi. They were tested for expression of resistance to different species of mycorrhizal fungi and to a fungal pathogen of tobacco, Thielaviopsis basicola , by monitoring the production of callose, phenolic compounds and peroxidases in dual cultures. Tobacco cells reacted to the presence of all the mycorrhizal fungi with callose deposits, whereas callose was nearly always absent in tobacco cells inoculated with their pathogen T. basicola. The broad-host range ectomycorrhizal fungi Hebeloma crustuliniforme, Lac-caria laccata and Suilhis granulatus elicited less intense responses than did Hymenoscyphus ericae. The results obtained for phenolic production and peroxidase activity were consistently similar to those obtained for callose deposition. They showed that H. ericae , an endomycorrhizal symbiont of Ericaceae, was highly incompatible with tobacco cells and that the tobacco pathogen T. basicola did not elicit strong reactions in the cells of its host. In this paper, the possibility of utilizing callus cultures as a simple model system to study both the different degrees of compatibility and the early events of recognition between mycorrhizal fungi and their host or non-host plants is discussed. 相似文献
7.
Cristiana Iosef Claudio M. Martin Marat Slessarev Carolina Gillio-Meina Gediminas Cepinskas Victor K. M. Han Douglas D. Fraser 《Journal of cellular and molecular medicine》2023,27(1):141-157
Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients. 相似文献
8.
Genetic Diversity of Isolates of Glomus mosseae from Different Geographic Areas Detected by Vegetative Compatibility Testing and Biochemical and Molecular Analysis
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Manuela Giovannetti Cristiana Sbrana Patrizia Strani Monica Agnolucci Valeria Rinaudo Luciano Avio 《Applied microbiology》2003,69(1):616-624
We detected, for the first time, the occurrence of vegetative incompatibility between different isolates of the arbuscular mycorrhizal fungal species Glomus mosseae. Vegetative compatibility tests performed on germlings belonging to the same isolate showed that six geographically different isolates were capable of self-anastomosing, and that the percentage of hyphal contacts leading to fusions ranged from 60 to 85%. Successful anastomoses were characterized by complete fusion of hyphal walls, protoplasm continuity and occurrence of nuclei in the middle of hyphal bridges. No anastomoses could be detected between hyphae belonging to different isolates, which intersected without any reaction in 49 to 68% of contacts. Microscopic examinations detected hyphal incompatibility responses in diverse pairings, consisting of protoplasm retraction from the tips and septum formation in the approaching hyphae, even before physical contact with neighboring hyphae. Interestingly, many hyphal tips showed precontact tropism, suggesting that specific recognition signals may be involved during this stage. The intraspecific genetic diversity of G. mosseae revealed by vegetative compatibility tests was confirmed by total protein profiles and internal transcribed spacer-restriction fragment length polymorphism profiles, which evidenced a higher level of molecular diversity between the two European isolates IMA1 and BEG25 than between IMA1 and the two American isolates. Since arbuscular mycorrhizal fungi lack a tractable genetic system, vegetative compatibility tests may represent an easy assay for the detection of genetically different mycelia and an additional powerful tool for investigating the population structure and genetics of these obligate symbionts. 相似文献
9.
Base pairing between U3 and the pre-ribosomal RNA is required for 18S rRNA synthesis. 总被引:34,自引:1,他引:33
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The nucleolus, the site of pre-ribosomal RNA (pre-rRNA) synthesis and processing in eukaryotic cells, contains a number of small nucleolar RNAs (snoRNAs). Yeast U3 snoRNA is required for the processing of 18S rRNA from larger precursors and contains a region complementary to the pre-rRNA. Substitution mutations in the pre-rRNA which disrupt this base pairing potential are lethal and prevent synthesis of 18S rRNA. These mutant pre-rRNAs show defects in processing which closely resemble the effects of genetic depletion of components of the U3 snoRNP. Co-expression of U3 snoRNAs which carry compensatory mutations allows the mutant pre-rRNAs to support viability and synthesize 18S rRNA at high levels. Pre-rRNA processing steps which are blocked by the external transcribed spacer region mutations are largely restored by expression of the compensatory U3 mutants. Pre-rRNA processing therefore requires direct base pairing between snoRNA and the substrate. Base pairing with the substrate is thus a common feature of small RNAs involved in mRNA and rRNA maturation. 相似文献
10.
Gloria Taliani Martina Spaziante Elisa Biliotti Marina Borro Donatella Palazzo Stefania Grieco Cristiana Franchi Giancarlo Iaiani Caterina Furlan Valentina Gallinaro Maurizio Simmaco 《PloS one》2013,8(8)