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排序方式: 共有158条查询结果,搜索用时 93 毫秒
131.
Garnett MJ Edelman EJ Heidorn SJ Greenman CD Dastur A Lau KW Greninger P Thompson IR Luo X Soares J Liu Q Iorio F Surdez D Chen L Milano RJ Bignell GR Tam AT Davies H Stevenson JA Barthorpe S Lutz SR Kogera F Lawrence K McLaren-Douglas A Mitropoulos X Mironenko T Thi H Richardson L Zhou W Jewitt F Zhang T O'Brien P Boisvert JL Price S Hur W Yang W Deng X Butler A Choi HG Chang JW Baselga J Stamenkovic I Engelman JA Sharma SV Delattre O Saez-Rodriguez J Gray NS Settleman J Futreal PA Haber DA 《Nature》2012,483(7391):570-575
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. 相似文献
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133.
Klaus Regenauer-Lieb Andrew Bunger Hui Tong Chua Arcady Dyskin Florian Fusseis Oliver Gaede Rob Jeffrey Ali Karrech Thomas Kohl Jie Liu Vladimir Lyakhovsky Elena Pasternak Robert Podgorney Thomas Poulet Sheik Rahman Christoph Schrank Mike Trefry Manolis Veveakis Bisheng Wu David A. Yuen Florian Wellmann Xi Zhang 《地球科学学刊》2015,(1)
Deep geothermal from the hot crystalline basement has remained an unsolved frontier for the geothermal industry for the past 30 years. This poses the challenge for developing a new un-conventional geom... 相似文献
134.
135.
Specialized DNA polymerases (DNA pols) are required for lesion bypass in human cells. Auxiliary factors have an important, but so far poorly understood, role. Here we analyse the effects of human proliferating cell nuclear antigen (PCNA) and replication protein A (RP-A) on six different human DNA pols--belonging to the B, Y and X classes--during in vitro bypass of different lesions. The mutagenic lesion 8-oxo-guanine (8-oxo-G) has high miscoding potential. A major and specific effect was found for 8-oxo-G bypass with DNA pols lambda and eta. PCNA and RP-A allowed correct incorporation of dCTP opposite a 8-oxo-G template 1,200-fold more efficiently than the incorrect dATP by DNA pol lambda, and 68-fold by DNA pol eta, respectively. Experiments with DNA-pol-lambda-null cell extracts suggested an important role for DNA pol lambda. On the other hand, DNA pol iota, together with DNA pols alpha, delta and beta, showed a much lower correct bypass efficiency. Our findings show the existence of an accurate mechanism to reduce the deleterious consequences of oxidative damage and, in addition, point to an important role for PCNA and RP-A in determining a functional hierarchy among different DNA pols in lesion bypass. 相似文献
136.
Rivalan P Delmas V Angulo E Bull LS Hall RJ Courchamp F Rosser AM Leader-Williams N 《Nature》2007,447(7144):529-530
137.
Simon S. Gerber Sofia Lejon Michael Locher Johann Schaller 《Cellular and molecular life sciences : CMLS》2010,67(9):1505-1518
The human α2-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities.
The C-terminal segment, A2PIC (Asn398-Lys452), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen,
of which four (Lys422, Lys429, Lys436, Lys452) are completely and two (Lys406, Lys415) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We
were able to identify the C-terminal Lys452 as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative,
zipper-like enhancement of the interaction between C-terminal Lys452 and internal Lys436 of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding
process. Sulfated Tyr445 in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains. 相似文献
138.
Parma P Radi O Vidal V Chaboissier MC Dellambra E Valentini S Guerra L Schedl A Camerino G 《Nature genetics》2006,38(11):1304-1309
R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY. 相似文献
139.
Cortina C Palomo-Ponce S Iglesias M Fernández-Masip JL Vivancos A Whissell G Humà M Peiró N Gallego L Jonkheer S Davy A Lloreta J Sancho E Batlle E 《Nature genetics》2007,39(11):1376-1383
The genes encoding tyrosine kinase receptors EphB2 and EphB3 are beta-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis. In CRC, EphB activity suppresses tumor progression beyond the earliest stages. Here we show that EphB receptors compartmentalize the expansion of CRC cells through a mechanism dependent on E-cadherin-mediated adhesion. We demonstrate that EphB-mediated compartmentalization restricts the spreading of EphB-expressing tumor cells into ephrin-B1-positive territories in vitro and in vivo. Our results indicate that CRC cells must silence EphB expression to avoid repulsive interactions imposed by normal ephrin-B1-expressing intestinal cells at the onset of tumorigenesis. 相似文献
140.
The crustaceans of the fresh waters of Bering Island and their link to the fauna of adjacent regions were studied. Based on original data and existing literature, the species composition of Cladocera and Copepoda was described. The compiled list includes 22 species of Cladocera and 30 species of Copepoda. In the original data, 35 species native to the Commander Islands were reported for the first time. Six species were newly reported in the Far East, and two were newly reported in Russia. The ecological peculiarities of several species and some biogeographical features of the freshwater zooplankton of the island are discussed. The main part of the fauna of the island form Holarctic widespread species (64.3%), another slightly smaller group of the fauna is comprised of Palaearctic species (20.1%), and the remainder comprise Nearctic (6.7%) and Beringian species (8.9%). Particular patterns in the distribution of freshwater zooplankton and the factors underlying the occurrence of these species on the island are considered. 相似文献