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排序方式: 共有139条查询结果,搜索用时 15 毫秒
51.
Pluchino S Zanotti L Rossi B Brambilla E Ottoboni L Salani G Martinello M Cattalini A Bergami A Furlan R Comi G Constantin G Martino G 《Nature》2005,436(7048):266-271
In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection. 相似文献
52.
53.
Sahin E Colla S Liesa M Moslehi J Müller FL Guo M Cooper M Kotton D Fabian AJ Walkey C Maser RS Tonon G Foerster F Xiong R Wang YA Shukla SA Jaskelioff M Martin ES Heffernan TP Protopopov A Ivanova E Mahoney JE Kost-Alimova M Perry SR Bronson R Liao R Mulligan R Shirihai OS Chin L DePinho RA 《Nature》2011,470(7334):359-365
54.
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts 总被引:2,自引:0,他引:2
55.
Elena Galfrè Lauretta Galeno Oscar Moran 《Cellular and molecular life sciences : CMLS》2012,69(21):3701-3713
Nucleotide binding domains (NBD1 and NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, are responsible for controlling the gating of the chloride channel and are the putative binding sites for several candidate drugs in the disease treatment. We studied the effects of the application of 2-pyrimidin-7,8-benzoflavone (PBF), a strong potentiator of the CFTR, on the properties of recombinant and equimolar NBD1/NBD2 mixture in solution. The results indicate that the potentiator induces significant conformational changes of the NBD1/NBD2 dimer in solution. The potentiator does not modify the ATP binding constant, but reduces the ATP hydrolysis activity of the NBD1/NBD2 mixture. The intrinsic fluorescence and the guanidinium denaturation measurements indicate that the potentiator induces different conformational changes on the NBD1/NBD2 mixture in the presence and absence of ATP. It was confirmed from small-angle X-ray scattering experiments that, in absence of ATP, the NBD1/NBD2 dimer was disrupted by the potentiator, but in the presence of 2?mM ATP, the two NBDs kept dimerised, and a major change in the size and the shape of the structure was observed. We propose that these conformational changes could modify the NBDs–intracellular loop interaction in a way that would facilitate the open state of the channel. 相似文献
56.
Francesca Cherubino Andreea Miszner Maria Daniela Renna Rachele Sangaletti Stefano Giovannardi Elena Bossi 《Cellular and molecular life sciences : CMLS》2009,66(23):3797-3808
The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied
with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (γ-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated
current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially
unaffected. The efficacy of desipramine, but not of the other drugs, is strongly increased in the lysine-glutamate or -aspartate
mutants K448E and K448D. Comparison of I
max and K
0.5GABA in the absence and presence of desipramine showed that both parameters are reduced by the drug in the wild-type and in the
K448E mutant. This suggests an uncompetitive inhibition, in which the drug can bind only after the substrate, an explanation
in agreement with the lack of effects on the pre-steady-state and leak currents, and with the known structural data. 相似文献
57.
58.
Solutions for a cultivated planet 总被引:61,自引:0,他引:61
Foley JA Ramankutty N Brauman KA Cassidy ES Gerber JS Johnston M Mueller ND O'Connell C Ray DK West PC Balzer C Bennett EM Carpenter SR Hill J Monfreda C Polasky S Rockström J Sheehan J Siebert S Tilman D Zaks DP 《Nature》2011,478(7369):337-342
Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture. 相似文献
59.
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass
60.
Gallo EM Winslow MM Canté-Barrett K Radermacher AN Ho L McGinnis L Iritani B Neilson JR Crabtree GR 《Nature》2007,450(7170):731-735
At critical times in development, cells are able to convert graded signals into discrete developmental outcomes; however, the mechanisms involved are poorly understood. During thymocyte development, cell fate is determined by signals originating from the alphabeta T-cell receptor. Low-affinity/avidity interactions between the T-cell receptor and peptide-MHC complexes direct differentiation to the single-positive stage (positive selection), whereas high-affinity/avidity interactions induce death by apoptosis (negative selection). Here we show that mice deficient in both calcineurin and nuclear factor of activated T cells (NFAT)c2/c3 lack a population of preselection thymocytes with enhanced ability to activate the mitogen-activated protein kinase (Raf-MEK-ERK) pathway, and fail to undergo positive selection. This defect can be partially rescued with constitutively active Raf, indicating that calcineurin controls MAPK signalling. Analysis of mice deficient in both Bim (which is required for negative selection) and calcineurin revealed that calcineurin-induced ERK (extracellular signal-regulated kinase) sensitization is required for differentiation in response to 'weak' positive selecting signals but not in response to 'strong' negative selecting signals (which normally induce apoptosis). These results indicate that early calcineurin/NFAT signalling produces a developmental period of ERK hypersensitivity, allowing very weak signals to induce positive selection. This mechanism might be generally useful in the discrimination of graded signals that induce different cell fates. 相似文献