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排序方式: 共有139条查询结果,搜索用时 265 毫秒
51.
Kozyrev SV Abelson AK Wojcik J Zaghlool A Linga Reddy MP Sanchez E Gunnarsson I Svenungsson E Sturfelt G Jönsen A Truedsson L Pons-Estel BA Witte T D'Alfonso S Barrizzone N Danieli MG Gutierrez C Suarez A Junker P Laustrup H Francisca González-Escribano M Martin J Abderrahim H Alarcón-Riquelme ME 《Nature genetics》2008,40(4):484
52.
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
53.
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase 总被引:2,自引:0,他引:2
Bryant HE Schultz N Thomas HD Parker KM Flower D Lopez E Kyle S Meuth M Curtin NJ Helleday T 《Nature》2005,434(7035):913-917
Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger gamma-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient cells, as a result of their deficiency in homologous recombination, are acutely sensitive to PARP inhibitors, presumably because resultant collapsed replication forks are no longer repaired. Thus, PARP1 activity is essential in homologous recombination-deficient BRCA2 mutant cells. We exploit this requirement in order to kill BRCA2-deficient tumours by PARP inhibition alone. Treatment with PARP inhibitors is likely to be highly tumour specific, because only the tumours (which are BRCA2-/-) in BRCA2+/- patients are defective in homologous recombination. The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment. 相似文献
54.
55.
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
56.
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts 总被引:2,自引:0,他引:2
57.
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
58.
Driving involves long hours of physical work within c onfined compartment. Taxi drivers usually work with prolonged working hours, add itional stress may likely be induced on particular body limbs. Occupational heal th may occur and working efficiency may potentially be affected resulting fr om fatigues, pains or diseases. These problems, however, could be remedied if mo re attention is paid on seating design, the workplace and driving postures adopt ed. Ergonomics design can provide better understanding... 相似文献
59.
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
60.
以长江口滨海湿地为研究区域,采用随机森林算法对滨海湿地植被进行分类。在提取Landsat?8 OLI影像植被指数和水体指数的基础上,提出利用植被指数季节差值对模型进行特征变量优化,分析了长江口滨海湿地植物群落分布的空间特征。以所占面积最大的互花米草(入侵物种)为例,采用多元线性回归模型结合实地测量数据,估算了秋季的互花米草植物密度的空间特征。提出的多时相遥感数据结合随机森林特征变量优化方法,可以较为便捷地提取长江口湿地3种优势物种的空间分布特征,与最大似然法相比,分类精度有较大提高,总体分类精度由78.35%提高至87.55%,Kappa系数由0.72提高至0.84。该方法适用于存在“异物同谱”问题的湿地植物群落研究。 相似文献