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排序方式: 共有149条查询结果,搜索用时 125 毫秒
111.
Gömez-Casado E Martínez-Lasot J Castro MJ Morales P Trápaga J Berciano M Lowy E Arnaiz-Villena A 《Cellular and molecular life sciences : CMLS》1999,56(3-4):356-362
HLA-E and -G genes show a restricted polymorphism encoding for molecules whose variability is limited at the peptide binding
site. Fourteen alleles that give rise to only three productive proteins for HLA-G (*0101, *0103 and *0104) and five alleles
with three different proteins for HLA-E (*0101, *0102 and *0103) have been described. Expression of these molecules is low
and found in many tissues for HLA-E; HLA-G protein is expressed in extravillous trophoblast cells and thymic epithelium. Molecular
studies have shown how HLA-G and HLA-E bind to natural killer (NK) cells immunoglobulin and lectin-type inhibitory receptors.
HLA-E may act as a sentinel of the cell; if classical class I and HLA-G are being expressed, HLA-E molecules may reach the
cell surface and inhibit the lysis by NK cells. Most findings are consistent with the hypothesis that HLA-E and -G proteins
may be tolerogenic molecules at either the T-cell receptor (TcR) (inflammation, graft rejection) or NK level, switching off
cells which usually attack foreign (including foetus) or self (autoimmune) antigens. A low HLA-E and -G polymorphism is observed
in humans, and their allele frequencies are mostly homogeneous in the populations tested so far. Many studies to detect these
alleles are now being performed in isolated populations and also in pregnancy-associated pathologies. In the present paper,
standard and detailed techniques to detect HLA-E and -G DNA polymorphism are reported and discussed.
Received 14 July 1999; received after revision 25 August 1999; accepted 25 August 1999 相似文献
112.
Graupera M Guillermet-Guibert J Foukas LC Phng LK Cain RJ Salpekar A Pearce W Meek S Millan J Cutillas PR Smith AJ Ridley AJ Ruhrberg C Gerhardt H Vanhaesebroeck B 《Nature》2008,453(7195):662-666
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis. 相似文献
113.
Quantification of digoxin by enzyme immunoassay: synthesis of a maleimide derivative of digoxigenin succinate for enzyme coupling 总被引:1,自引:0,他引:1
Summary We synthesized the m-maleimidobenzoyl derivative of digoxigenin-3-0-succinate (through a p-phenylenediamine bridge) as a hapten derivative directed towards coupling to sulfhydryl groups of -galactosidase. Prepared enzyme conjugate had about 97% of the enzyme labeled with the hapten derivative while retaining full enzyme activity. The enzyme immunoassay for digoxin we prepared showed a maximum sensitivity of 30 pg per assay (c.v.=3%) with minimal cross-reaction with digotoxin (3.8%). Our method for hapten conjugation to -galactosidase is highly efficient and is simple and easily replicated. 相似文献
114.
115.
The d-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While l-amino acids clearly predominate in nature, d-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and d-Ala and d-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that d-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize
and release d-amino acids, including d-Met and d-Leu, which were not previously known to be made. These noncanonical d-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities.
Elucidating the mechanisms by which d-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how
extracytoplasmic processes are regulated as well as lead to development of novel therapeutics. 相似文献
116.
Hu TT Pattyn P Bakker EG Cao J Cheng JF Clark RM Fahlgren N Fawcett JA Grimwood J Gundlach H Haberer G Hollister JD Ossowski S Ottilar RP Salamov AA Schneeberger K Spannagl M Wang X Yang L Nasrallah ME Bergelson J Carrington JC Gaut BS Schmutz J Mayer KF Van de Peer Y Grigoriev IV Nordborg M Weigel D Guo YL 《Nature genetics》2011,43(5):476-481
We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged from A. lyrata 10 million years ago, likely constitutes the derived state for the family. We found evidence for DNA loss from large-scale rearrangements, but most of the difference in genome size can be attributed to hundreds of thousands of small deletions, mostly in noncoding DNA and transposons. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome. The high-quality reference genome sequence for A. lyrata will be an important resource for functional, evolutionary and ecological studies in the genus Arabidopsis. 相似文献
117.
Ignacio Campillo-Marcos Pedro A. Lazo 《Cellular and molecular life sciences : CMLS》2018,75(13):2375-2388
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage. 相似文献
118.
Jaeger E Leedham S Lewis A Segditsas S Becker M Cuadrado PR Davis H Kaur K Heinimann K Howarth K East J Taylor J Thomas H Tomlinson I 《Nature genetics》2012,44(6):699-703
Hereditary mixed polyposis syndrome (HMPS) is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This unusual mutation is associated with increased allele-specific GREM1 expression. Whereas GREM1 is expressed in intestinal subepithelial myofibroblasts in controls, GREM1 is predominantly expressed in the epithelium of the large bowel in individuals with HMPS. The HMPS duplication contains predicted enhancer elements; some of these interact with the GREM1 promoter and can drive gene expression in vitro. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein (BMP) pathway activity, a mechanism that also underlies tumorigenesis in juvenile polyposis of the large bowel. 相似文献
119.
Quesada V Conde L Villamor N Ordóñez GR Jares P Bassaganyas L Ramsay AJ Beà S Pinyol M Martínez-Trillos A López-Guerra M Colomer D Navarro A Baumann T Aymerich M Rozman M Delgado J Giné E Hernández JM González-Díaz M Puente DA Velasco G Freije JM Tubío JM Royo R Gelpí JL Orozco M Pisano DG Zamora J Vázquez M Valencia A Himmelbauer H Bayés M Heath S Gut M Gut I Estivill X López-Guillermo A Puente XS Campo E López-Otín C 《Nature genetics》2012,44(1):47-52
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies. 相似文献
120.
Humberto Godínez‐Olivares María del Carmen Boado‐Penas Athanasios A. Pantelous 《Journal of forecasting》2016,35(1):13-33
The aim of this paper was to design optimal strategies using nonlinear dynamic programming to guarantee the required level of liquidity in pay‐as‐you‐go pension systems through changes in the key variables of the system, such as the contribution rate, retirement age and/or indexation of pensions. These strategies, also known as automatic balancing mechanisms (ABMs), calculate the optimal path of these variables over time, managing fluctuations in longevity, fertility rates, salary growth or any other kind of uncertainty faced by the pension scheme without repeated legislative intervention. A numerical application of our model, which uses the projection of the population structure of two representative countries, illustrates the main findings of the paper. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献