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排序方式: 共有334条查询结果,搜索用时 31 毫秒
91.
Ellinghaus E Ellinghaus D Stuart PE Nair RP Debrus S Raelson JV Belouchi M Fournier H Reinhard C Ding J Li Y Tejasvi T Gudjonsson J Stoll SW Voorhees JJ Lambert S Weidinger S Eberlein B Kunz M Rahman P Gladman DD Gieger C Wichmann HE Karlsen TH Mayr G Albrecht M Kabelitz D Mrowietz U Abecasis GR Elder JT Schreiber S Weichenthal M Franke A 《Nature genetics》2010,42(11):991-995
92.
Zanke BW Greenwood CM Rangrej J Kustra R Tenesa A Farrington SM Prendergast J Olschwang S Chiang T Crowdy E Ferretti V Laflamme P Sundararajan S Roumy S Olivier JF Robidoux F Sladek R Montpetit A Campbell P Bezieau S O'Shea AM Zogopoulos G Cotterchio M Newcomb P McLaughlin J Younghusband B Green R Green J Porteous ME Campbell H Blanche H Sahbatou M Tubacher E Bonaiti-Pellié C Buecher B Riboli E Kury S Chanock SJ Potter J Thomas G Gallinger S Hudson TJ Dunlop MG 《Nature genetics》2007,39(8):989-994
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer. 相似文献
93.
Weedon MN Lettre G Freathy RM Lindgren CM Voight BF Perry JR Elliott KS Hackett R Guiducci C Shields B Zeggini E Lango H Lyssenko V Timpson NJ Burtt NP Rayner NW Saxena R Ardlie K Tobias JH Ness AR Ring SM Palmer CN Morris AD Peltonen L Salomaa V;Diabetes Genetics Initiative;Wellcome Trust Case Control Consortium Davey Smith G Groop LC Hattersley AT McCarthy MI Hirschhorn JN Frayling TM 《Nature genetics》2007,39(10):1245-1250
Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P = 4 x 10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P = 3 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height. 相似文献
94.
Spontaneous DNA breakage in single living Escherichia coli cells 总被引:3,自引:0,他引:3
Spontaneous DNA breakage is predicted to be a frequent, inevitable consequence of DNA replication and is thought to underlie much of the genomic change that fuels cancer and evolution. Despite its importance, there has been little direct measurement of the amounts, types, sources and fates of spontaneous DNA lesions in living cells. We present a direct, sensitive flow cytometric assay in single living Escherichia coli cells for DNA lesions capable of inducing the SOS DNA damage response, and we report its use in quantification of spontaneous DNA double-strand breaks (DSBs). We report efficient detection of single chromosomal DSBs and rates of spontaneous breakage approximately 20- to 100-fold lower than predicted. In addition, we implicate DNA replication in the origin of spontaneous DSBs with the finding of fewer spontaneous DSBs in a mutant with altered DNA polymerase III. The data imply that spontaneous DSBs induce genomic changes and instability 20-100 times more potently than previously appreciated. Finally, FACS demonstrated two main cell fates after spontaneous DNA damage: viability with or without resumption of proliferation. 相似文献
95.
Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth 总被引:2,自引:0,他引:2
Douglas J Cilliers D Coleman K Tatton-Brown K Barker K Bernhard B Burn J Huson S Josifova D Lacombe D Malik M Mansour S Reid E Cormier-Daire V Cole T;Childhood Overgrowth Collaboration Rahman N 《Nature genetics》2007,39(8):963-965
17q11 microdeletions that encompass NF1 cause 5%-10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is within the NF1 microdeletion region, in six families characterized by overgrowth, learning disability, dysmorphic features and variable additional features. These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases. 相似文献
96.
97.
98.
Yasmina?Manso Javier?Carrasco Gemma?Comes Gabriele?Meloni Paul?A.?Adlard Ashley?I.?Bush Milan?Va?ák Juan?HidalgoEmail author 《Cellular and molecular life sciences : CMLS》2012,69(21):3683-3700
Among the dementias, Alzheimer’s disease (AD) is the most commonly diagnosed, but there are still no effective drugs available for its treatment. It has been suggested that metallothionein-3 (MT-3) could be somehow involved in the etiology of AD, and in fact very promising results have been found in in vitro studies, but the role of MT-3 in vivo needs further analysis. In this study, we analyzed the role of MT-3 in a mouse model of AD, Tg2576 mice, which overexpress human Amyloid Precursor Protein (hAPP) with the Swedish mutation. MT-3 deficiency partially rescued the APP-induced mortality of females, and mildly affected APP-induced changes in behavior assessed in the hole-board and plus-maze tests in a gender-dependent manner. Amyloid plaque burden and/or hAPP expression were decreased in the cortex and hippocampus of MT-3-deficient females. Interestingly, exogenously administered Zn7MT-3 increased soluble Aβ40 and Aβ42 and amyloid plaques and gliosis, particularly in the cortex, and changed several behavioral traits (increased deambulation and exploration and decreased anxiety). These results highlight that the control of the endogenous production and/or action of MT-3 could represent a powerful therapeutic target in AD. 相似文献
99.
Davies WI Wilkie SE Cowing JA Hankins MW Hunt DM 《Cellular and molecular life sciences : CMLS》2012,69(14):2455-2464
The long-wavelength-sensitive (LWS) opsins form one of four classes of vertebrate cone visual pigment and exhibit peak spectral sensitivities (λ(max)) that generally range from 525 to 560 nm for rhodopsin/vitamin-A(1) photopigments. Unique amongst the opsin classes, many LWS pigments show anion sensitivity through the interaction of chloride ions with a histidine residue at site 197 (H197) to give a long-wavelength spectral shift in peak sensitivity. Although it has been shown that amino acid substitutions at five sites (180, 197, 277, 285 and 308) are useful in predicting the λ(max) values of the LWS pigment class, some species, such as the elephant shark and most marine mammals, express LWS opsins that possess λ(max) values that are not consistent with this 'five-site' rule, indicating that other interactions may be involved. This study has taken advantage of the natural mutation at the chloride-binding site in the mouse LWS pigment. Through the use of a number of mutant pigments generated by site-directed mutagenesis, a new model has been formulated that takes into account the role of charge and steric properties of the side chains of residues at sites 197 and 308 in the function of the chloride-binding site in determining the peak sensitivity of LWS photopigments. 相似文献