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排序方式: 共有289条查询结果,搜索用时 15 毫秒
231.
232.
Thomas RK Baker AC Debiasi RM Winckler W Laframboise T Lin WM Wang M Feng W Zander T MacConaill L Macconnaill LE Lee JC Nicoletti R Hatton C Goyette M Girard L Majmudar K Ziaugra L Wong KK Gabriel S Beroukhim R Peyton M Barretina J Dutt A Emery C Greulich H Shah K Sasaki H Gazdar A Minna J Armstrong SA Mellinghoff IK Hodi FS Dranoff G Mischel PS Cloughesy TF Nelson SF Liau LM Mertz K Rubin MA Moch H Loda M Catalona W Fletcher J Signoretti S Kaye F Anderson KC Demetri GD Dummer R Wagner S 《Nature genetics》2007,39(3):347-351
Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention. 相似文献
233.
Roscioli T Cliffe ST Bloch DB Bell CG Mullan G Taylor PJ Sarris M Wang J Donald JA Kirk EP Ziegler JB Salzer U McDonald GB Wong M Lindeman R Buckley MF 《Nature genetics》2006,38(6):620-622
We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency, an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease. This is the first report of the involvement of a nuclear body protein in a human primary immunodeficiency and of high-penetrance genetic mutations in hepatic veno-occlusive disease. 相似文献
234.
Gerlach B Cordier SM Schmukle AC Emmerich CH Rieser E Haas TL Webb AI Rickard JA Anderton H Wong WW Nachbur U Gangoda L Warnken U Purcell AW Silke J Walczak H 《Nature》2011,471(7340):591-596
Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKγ or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1β was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling. 相似文献
235.
Keane TM Goodstadt L Danecek P White MA Wong K Yalcin B Heger A Agam A Slater G Goodson M Furlotte NA Eskin E Nellåker C Whitley H Cleak J Janowitz D Hernandez-Pliego P Edwards A Belgard TG Oliver PL McIntyre RE Bhomra A Nicod J Gan X Yuan W van der Weyden L Steward CA Bala S Stalker J Mott R Durbin R Jackson IJ Czechanski A Guerra-Assunção JA Donahue LR Reinholdt LG Payseur BA Ponting CP Birney E Flint J Adams DJ 《Nature》2011,477(7364):289-294
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237.
In order to compete in the global manufacturing mar ke t, agility is the only possible solution to response to the fragmented market se gments and frequently changed customer requirements. However, manufacturing agil ity can only be attained through the deployment of knowledge. To embed knowledge into a CAD system to form a knowledge intensive CAD (KIC) system is one of way to enhance the design compatibility of a manufacturing company. The most difficu lt phase to develop a KIC system is to capitalize a ... 相似文献
238.
王鸿 《东莞理工学院学报》2003,10(1):68-72,78
推广普通话是我国的一项基本国策。在我国普及普通话,提高普通话水平,关键是提高教师和相关专业不的普通话水平。这是关系到加强中华民族凝聚力和提高全体人民素质的紧迫任务,我们必须加强学习和宣传工作,破除“语音面貌定局论”、“方言难改论”的思想障碍,采取有效措施,加强训练,在较短的时间内切实提高普通话的水平。 相似文献
239.
A total of 110 primary NSCLCs (non-small cell lung cancers) were recruited in this study to characterize the pattern of 3p21
LOH together with the RASSF1A methylation status and their clinical implication. 3p21 LOH by 8 microsatellite markers, RASSF1A
methylation status by methylation-specific PCR (MSPCR) as well as bisulfite genomic sequencing (BGS), and RASSF1A expression
level by real-time quantitative PCR was performed. 3p21 LOH is frequent in NSCLC with a mean frequency of (41.2±3.7)%. Significant
associations between 3p21 LOH and gender, smoking history, histological type, and tumor size were observed. Cases with LOH
have a slightly lower RASSF1A expression than cases without LOH but not statistically significant. Comparison of RASSF1A methylation
that resulted from the three analyses shows significant correlations from one another. Higher frequency of methylation was
observed in larger tumors and in smokers compared with smaller tumors and non-smokers, respectively. A significant correlation
was also observed in extent between methylation and RASSF1A expression, illustrating that epigenetic mechanism could affect
gene expression. The significant clinicopathological relations of 3p21 LOH may be of great use for both early detection and
therapeutic interventions. 相似文献
240.
国际竞争的实质是人才的竞争。加强素质教育,培养创新人才是时代赋予教育的神圣职责。教育工作者要更新教育观念,充分尊重学生的主体性。 相似文献