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排序方式: 共有164条查询结果,搜索用时 15 毫秒
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Heffelfinger GS Martino A Gorin A Xu Y Rintoul MD Geist A Al-Hashimi HM Davidson GS Faulon JL Frink LJ Haaland DM Hart WE Jakobsson E Lane T Li M Locascio P Olken F Olman V Palenik B Plimpton SJ Roe DC Samatova NF Shah M Shoshoni A Strauss CE Thomas EV Timlin JA Xu D 《Omics : a journal of integrative biology》2002,6(4):305-330
The U.S. Department of Energy recently announced the first five grants for the Genomes to Life (GTL) Program. The goal of this program is to "achieve the most far-reaching of all biological goals: a fundamental, comprehensive, and systematic understanding of life." While more information about the program can be found at the GTL website (www.doegenomestolife.org), this paper provides an overview of one of the five GTL projects funded, "Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling." This project is a combined experimental and computational effort emphasizing developing, prototyping, and applying new computational tools and methods to elucidate the biochemical mechanisms of the carbon sequestration of Synechococcus Sp., an abundant marine cyanobacteria known to play an important role in the global carbon cycle. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a major focus of biological oceanography and has more recently been of interest to a broader audience of scientists and policy makers. It is clear that the oceanic sinks and sources of CO(2) are important terms in the global environmental response to anthropogenic atmospheric inputs of CO(2) and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon fixation in these microorganisms is poorly understood. The project includes five subprojects: an experimental investigation, three computational biology efforts, and a fifth which deals with addressing computational infrastructure challenges of relevance to this project and the Genomes to Life program as a whole. Our experimental effort is designed to provide biology and data to drive the computational efforts and includes significant investment in developing new experimental methods for uncovering protein partners, characterizing protein complexes, identifying new binding domains. We will also develop and apply new data measurement and statistical methods for analyzing microarray experiments. Our computational efforts include coupling molecular simulation methods with knowledge discovery from diverse biological data sets for high-throughput discovery and characterization of protein-protein complexes and developing a set of novel capabilities for inference of regulatory pathways in microbial genomes across multiple sources of information through the integration of computational and experimental technologies. These capabilities will be applied to Synechococcus regulatory pathways to characterize their interaction map and identify component proteins in these pathways. We will also investigate methods for combining experimental and computational results with visualization and natural language tools to accelerate discovery of regulatory pathways. Furthermore, given that the ultimate goal of this effort is to develop a systems-level of understanding of how the Synechococcus genome affects carbon fixation at the global scale, we will develop and apply a set of tools for capturing the carbon fixation behavior of complex of Synechococcus at different levels of resolution. Finally, because the explosion of data being produced by high-throughput experiments requires data analysis and models which are more computationally complex, more heterogeneous, and require coupling to ever increasing amounts of experimentally obtained data in varying formats, we have also established a companion computational infrastructure to support this effort as well as the Genomes to Life program as a whole. 相似文献
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Glycosylation sites and site-specific glycosylation in human Tamm- Horsfall glycoprotein 总被引:4,自引:1,他引:3
The N-glycosylation sites of human Tamm-Horsfall glycoprotein from one
healthy male donor have been characterized, based on an approach using
endoproteinase Glu-C (V-8 protease, Staphylococcus aureus ) digestion and a
combination of chromatographic techniques, automated Edman sequencing, and
fast atom bombardment mass spectrometry. Seven out of the eight potential
N-glycosylation sites, namely, Asn52, Asn56, Asn208, Asn251, Asn298,
Asn372, and Asn489, turned out to be glycosylated, and the potential
glycosylation site at Asn14, being close to the N-terminus, is not used.
The carbohydrate microheterogeneity on three of the glycosylation sites was
studied in more detail by high-pH anion-exchange chromatographic profiling
and 500 MHz1H-NMR spectroscopy. Glycosylation site Asn489 contains mainly
di- and tri-charged oligosaccharides which comprise, among others, the
GalNAc4 S (beta1-4)GlcNAc terminal sequence. Only glycosylation site Asn251
bears oligomannose-type carbohydrate chains ranging from Man5GlcNAc2to
Man8GlcNAc2, in addition to a small amount of complex- type structures.
Profiling of the carbohydrate moieties of Asn208 indicates a large
heterogeneity, similar to that established for native human Tamm-Horsfall
glycoprotein, namely, multiply charged complex-type carbohydrate
structures, terminated by sulfate groups, sialic acid residues, and/or the
Sda-determinant.
相似文献
76.
Leo AB Joosten Erik Lubberts Monique MA Helsen Tore Saxne Christina JJ Coenen-de Roo Dick Heinegård Wim B van den Berg 《Arthritis research & therapy》1999,1(1):81-11
Destruction of cartilage and bone are hallmarks of human rheumatoid arthritis (RA), and controlling these erosive processes
is the most challenging objective in the treatment of RA. Systemic interleukin-4 treatment of established murine collagen-induced
arthritis suppressed disease activity and protected against cartilage and bone destruction. Reduced cartilage pathology was
confirmed by both decreased serum cartilage oligomeric matrix protein (COMP) and histological examination. In addition, radiological
analysis revealed that bone destruction was also partially prevented. Improved suppression of joint swelling was achieved
when interleukin-4 treatment was combined with low-dose prednisolone treatment. Interestingly, synergistic reduction of both
serum COMP and inflammatory parameters was noted when low-dose interleukin-4 was combined with prednisolone. Systemic treatment
with interleukin-4 appeared to be a protective therapy for cartilage and bone in arthritis, and in combination with prednisolone
at low dosages may offer an alternative therapy in RA. 相似文献
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M Barathan V Mariappan E M Shankar B JJ Abdullah K L Goh J Vadivelu 《Cell death & disease》2013,4(6):e697
Photodynamic therapy (PDT) has emerged as a capable therapeutic modality for the treatment of cancer. PDT is a targeted cancer therapy that reportedly leads to tumor cell apoptosis and/or necrosis by facilitating the secretion of certain pro-inflammatory cytokines and expression of multiple apoptotic mediators in the tumor microenvironment. In addition, PDT also triggers oxidative stress that directs tumor cell killing and activation of inflammatory responses. However, the cellular and molecular mechanisms underlying the role of PDT in facilitating tumor cell apoptosis remain ambiguous. Here, we investigated the ability of PDT in association with hypericin (HY) to induce tumor cell apoptosis by facilitating the induction of reactive oxygen species (ROS) and secretion of Th1/Th2/Th17 cytokines in human hepatocellular liver carcinoma cell line (HepG2) cells. To discover if any apoptotic mediators were implicated in the enhancement of cell death of HY-PDT-treated tumor cells, selected gene profiling in response to HY-PDT treatment was implemented. Experimental results showed that interleukin (IL)-6 was significantly increased in all HY-PDT-treated cells, especially in 1 μg/ml HY-PDT, resulting in cell death. In addition, quantitative real-time PCR analysis revealed that the expression of apoptotic genes, such as BH3-interacting-domain death agonist (BID), cytochrome complex (CYT-C) and caspases (CASP3, 6, 7, 8 and 9) was remarkably higher in HY-PDT-treated HepG2 cells than the untreated HepG2 cells, entailing that tumor destruction of immune-mediated cell death occurs only in PDT-treated tumor cells. Hence, we showed that HY-PDT treatment induces apoptosis in HepG2 cells by facilitating cytotoxic ROS, and potentially recruits IL-6 and apoptosis mediators, providing additional hints for the existence of alternative mechanisms of anti-tumor immunity in hepatocellular carcinoma, which contribute to long-term suppression of tumor growth following PDT. 相似文献