全文获取类型
收费全文 | 137篇 |
免费 | 3篇 |
专业分类
系统科学 | 10篇 |
理论与方法论 | 2篇 |
现状及发展 | 40篇 |
研究方法 | 21篇 |
综合类 | 52篇 |
自然研究 | 15篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 11篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 10篇 |
2011年 | 15篇 |
2010年 | 2篇 |
2008年 | 3篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 4篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1968年 | 4篇 |
1965年 | 5篇 |
1963年 | 1篇 |
1961年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有140条查询结果,搜索用时 162 毫秒
61.
Nelson Gomes de Oliveira Junior Marlon Henrique e Silva Cardoso Octavio Luiz Franco 《Cellular and molecular life sciences : CMLS》2013,70(24):4645-4658
Gram-positive and -negative bacteria are dangerous pathogens that may cause human infection diseases, especially due to the increasingly high prevalence of antibiotic resistance, which is becoming one of the most alarming clinical problems. In the search for novel antimicrobial compounds, snake venoms represent a rich source for such compounds, which are produced by specialized glands in the snake’s jawbone. Several venom compounds have been used for antimicrobial effects. Among them are phospholipases A2, which hydrolyze phospholipids and could act on bacterial cell surfaces. Moreover, metalloproteinases and l-amino acid oxidases, which represent important enzyme classes with antimicrobial properties, are investigated in this study. Finally, antimicrobial peptides from multiple classes are also found in snake venoms and will be mentioned. All these molecules have demonstrated an interesting alternative for controlling microorganisms that are resistant to conventional antibiotics, contributing in medicine due to their differential mechanisms of action and versatility. In this review, snake venom antimicrobial compounds will be focused on, including their enormous biotechnological applications for drug development. 相似文献
62.
McKern NM Lawrence MC Streltsov VA Lou MZ Adams TE Lovrecz GO Elleman TC Richards KM Bentley JD Pilling PA Hoyne PA Cartledge KA Pham TM Lewis JL Sankovich SE Stoichevska V Da Silva E Robinson CP Frenkel MJ Sparrow LG Fernley RT Epa VC Ward CW 《Nature》2006,443(7108):218-221
The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding. 相似文献
63.
Through cell fusion, embryonic stem (ES) cells can erase the developmental programming of differentiated cell nuclei and impose pluripotency. Molecules that mediate this conversion should be identifiable in ES cells. One candidate is the variant homeodomain protein Nanog, which has the capacity to entrain undifferentiated ES cell propagation. Here we report that in fusions between ES cells and neural stem (NS) cells, increased levels of Nanog stimulate pluripotent gene activation from the somatic cell genome and enable an up to 200-fold increase in the recovery of hybrid colonies, all of which show ES cell characteristics. Nanog also improves hybrid yield when thymocytes or fibroblasts are fused to ES cells; however, fewer colonies are obtained than from ES x NS cell fusions, consistent with a hierarchical susceptibility to reprogramming among somatic cell types. Notably, for NS x ES cell fusions elevated Nanog enables primary hybrids to develop into ES cell colonies with identical frequency to homotypic ES x ES fusion products. This means that in hybrids, increased Nanog is sufficient for the NS cell epigenome to be reset completely to a state of pluripotency. We conclude that Nanog can orchestrate ES cell machinery to instate pluripotency with an efficiency of up to 100% depending on the differentiation status of the somatic cell. 相似文献
64.
Shaw-Smith C Pittman AM Willatt L Martin H Rickman L Gribble S Curley R Cumming S Dunn C Kalaitzopoulos D Porter K Prigmore E Krepischi-Santos AC Varela MC Koiffmann CP Lees AJ Rosenberg C Firth HV de Silva R Carter NP 《Nature genetics》2006,38(9):1032-1037
Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination. 相似文献
65.
The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. 总被引:8,自引:0,他引:8
Laurent Gouya Herve Puy Anne-Marie Robreau Monique Bourgeois Jer?me Lamoril Vasco Da Silva Bernard Grandchamp Jean-Charles Deybach 《Nature genetics》2002,30(1):27-28
Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC 4.99.1.1). EPP is transmitted as an autosomal dominant disorder with an incomplete penetrance. Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3-48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression. 相似文献
66.
The genome of woodland strawberry (Fragaria vesca) 总被引:3,自引:0,他引:3
Shulaev V Sargent DJ Crowhurst RN Mockler TC Folkerts O Delcher AL Jaiswal P Mockaitis K Liston A Mane SP Burns P Davis TM Slovin JP Bassil N Hellens RP Evans C Harkins T Kodira C Desany B Crasta OR Jensen RV Allan AC Michael TP Setubal JC Celton JM Rees DJ Williams KP Holt SH Ruiz Rojas JJ Chatterjee M Liu B Silva H Meisel L Adato A Filichkin SA Troggio M Viola R Ashman TL Wang H Dharmawardhana P Elser J Raja R Priest HD Bryant DW Fox SE Givan SA Wilhelm LJ Naithani S Christoffels A Salama DY 《Nature genetics》2011,43(2):109-116
67.
María Catalina Ramírez Jaime Plazas Camilo Torres Juan Camilo Silva Luis Camilo Caicedo Miguel Angel González 《Systemic Practice and Action Research》2012,25(2):95-116
In several rural areas in Colombia there is a serious lack of water quality supply. Thereby the problematic situation is understood
as complex one that involves stakeholders with pluralistic interests, multiple variables and requires the development of sustainable
and suitable solutions. In order to address this issue, this paper proposes an integration of engineering design framework
(CDIO) with a systemic approach. Particularly the approach emphasizes on systemic elements such as autonomy, systems within
systems, cooperation between stakeholders and cause effect relations; it also proposes a previous observing phase for engineering
design framework. Thus the proposed systemic framework aims to generate projects that improve living conditions in rural communities
and promote the production of knowledge between the stakeholders to ensure sustainability in the long term. To illustrate
the proposal, this work contains a case study that discusses a project carried out by a research team—Ingenieros Sin Fronteras Colombia—in a rural district near to Colombia’s capital. The experience, which involved and benefited 16 families in the community,
provided strong evidence to support the proposed framework. The paper concludes with a discussion about the replication of
this proposal in other contexts. 相似文献
68.
Separability of clusters is an issue that arises in many different areas, and is often used in a rather vague and subjective
manner. We introduce a combinatorial notion of interiority to derive a global view on separability of a set of entities. We
develop this approach further to evaluate the overall separability of a partition in the context of cluster analysis. Our
approach captures combinatorial and geometrical aspects of data and provides, in addition to numerical evaluations, graphical
representations particularly useful when data are not easily visualized. We illustrate the methodology on some real and simulated
datasets. 相似文献
69.
70.
Natural killer (NK) cells have originally been identified by their spontaneous cytolytic potential against tumor cells, which,
however, might result from pre-activation due to prior pathogen exposure. Resting NK cells, on the contrary, require activation
by bystander antigen-presenting cells to reach their full functional competence. In this review, we will summarize studies
on how dendritic cells (DCs), the most potent type of antigen-presenting cell, communicate with human NK cells to activate
them in secondary lymphoid organs and to integrate signals from activated NK cells at sites of inflammation for their own
maturation. Furthermore, we will review aspects of the immunological synapse, which mediates this cross-talk. These studies
provide the mechanistic understanding of how mature DCs can activate NK cells and survive to go on for the activation of adaptive
immunity. This feature of DCs, to activate different waves of immune responses, could be harnessed for immunotherapies, including
vaccinations. 相似文献