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61.
J A Camacho C Obie B Biery B K Goodman C A Hu S Almashanu G Steel R Casey M Lambert G A Mitchell D Valle 《Nature genetics》1999,22(2):151-158
Neurospora crassa ARG13 and Saccharomyces cerevisiae ARG11 encode mitochondrial carrier family (MCF) proteins that transport ornithine across the mitochondrial inner membrane. We used their sequences to identify EST candidates that partially encode orthologous mammalian transporters. We thereby identified such a gene (ORNT1) that maps to 13q14 and whose expression, similar to that of other urea cycle (UC) components, was high in liver and varied with changes in dietary protein. ORNT1 expression restores ornithine metabolism in fibroblasts from patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH) syndrome. In a survey of 11 HHH probands, we identified 3 ORNT1 mutant alleles that account for 21 of 22 possible mutant ORNT1 genes in our patients: F188delta, which is common in French-Canadian HHH patients and encodes an unstable protein; E180K, which encodes a stable, properly targeted protein that is inactive; and a 13q14 microdeletion. Our results show that ORNT1 encodes the mitochondrial ornithine transporter involved in UC function and is defective in HHH syndrome. 相似文献
62.
Summary Yellow phenocopies ofDrosophila melanogaster were produced by raising larvae on -DMT contaminated media. Using a survivorship test, the sensitive period for phenocopy induction was found to occur during the third larval instar of development, with increased survivorship at 1% -DMT compared with lower concentrations. It was also found that treatment with -DMT significantly slowed development. These findings are related to the relevant morphological and behavioral developmental pathways and to phenocopy induction.Publication No. 35 from the Evolutionary Genetics Laboratory, University of Auckland.Acknowledgments. We thank the New Zealand Entomology Society for a grant from their Anniversary Fund to R. D. Newcomb and the University Grants Committee, Research Grant No. 394.597 to D.M. Lambert. 相似文献
63.
Astronomical observations of elemental and isotopic abundances provide the means to determine the source of elements and to reveal their evolutionary pathways since the formation of the Galaxy some 15 billion years ago. The abundance of lithium is particularly interesting because, although some of it is thought to be primordial, most results from spallation reactions (in which Galactic cosmic rays break apart larger nuclei in the interstellar medium). Spallation reactions are crucial for the production of other light elements, such as beryllium and boron, so observations of lithium isotopic abundances can be used to test model predictions for light-element synthesis in general. Here we report observations of 7Li and 6Li abundances in several interstellar clouds lying in the direction of the star o Persei. We find the abundance ratio 7Li/6Li to be about 2, which is significantly lower than the average Solar System value of 12.3 (refs 6, 7). An abundance ratio of 2 is clear evidence that the observed lithium must have resulted entirely from spallation, confirming a basic tenet of light-element synthesis. The total lithium abundance, however, is not enhanced as expected. 相似文献
64.
Selective oxidation with dioxygen by gold nanoparticle catalysts derived from 55-atom clusters 总被引:1,自引:0,他引:1
Turner M Golovko VB Vaughan OP Abdulkin P Berenguer-Murcia A Tikhov MS Johnson BF Lambert RM 《Nature》2008,454(7207):981-983
Supported gold nanoparticles have excited much interest owing to their unusual and somewhat unexpected catalytic properties, but the origin of the catalytic activity is still not fully understood. Experimental work on gold particles supported on a titanium dioxide (110) single-crystal surface has established a striking size threshold effect associated with a metal-to-insulator transition, with gold particles catalytically active only if their diameters fall below approximately 3.5 nm. However, the remarkable catalytic behaviour might also in part arise from strong electronic interaction between the gold and the titanium dioxide support. In the case of industrially important selective oxidation reactions, explanation of the effectiveness of gold nanoparticle catalysts is complicated by the need for additives to drive the reaction, and/or the presence of strong support interactions and incomplete understanding of their possible catalytic role. Here we show that very small gold entities ( approximately 1.4 nm) derived from 55-atom gold clusters and supported on inert materials are efficient and robust catalysts for the selective oxidation of styrene by dioxygen. We find a sharp size threshold in catalytic activity, in that particles with diameters of approximately 2 nm and above are completely inactive. Our observations suggest that catalytic activity arises from the altered electronic structure intrinsic to small gold nanoparticles, and that the use of 55-atom gold clusters may prove a viable route to the synthesis of robust gold catalysts suited to practical application. 相似文献
65.
Hollingworth P Harold D Sims R Gerrish A Lambert JC Carrasquillo MM Abraham R Hamshere ML Pahwa JS Moskvina V Dowzell K Jones N Stretton A Thomas C Richards A Ivanov D Widdowson C Chapman J Lovestone S Powell J Proitsi P Lupton MK Brayne C Rubinsztein DC Gill M Lawlor B Lynch A Brown KS Passmore PA Craig D McGuinness B Todd S Holmes C Mann D Smith AD Beaumont H Warden D Wilcock G Love S Kehoe PG Hooper NM Vardy ER Hardy J Mead S Fox NC Rossor M Collinge J Maier W Jessen F Rüther E Schürmann B 《Nature genetics》2011,43(5):429-435
We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)). 相似文献
66.
Zhang ZG Lambert CA Servotte S Chometon G Eckes B Krieg T Lapière CM Nusgens BV Aumailley M 《Cellular and molecular life sciences : CMLS》2006,63(1):82-91
The GTP-binding proteins RhoA, Cdc42 and Rac1 regulate the organization and turnover of the cytoskeleton and cell-matrix adhesions,
structures bridging cells to their support, and translating forces, external or generated within the cell. To investigate
the specific requirements of Rho GTPases for biomechanical activities of clonal cell populations, we compared side-by-side
stable lines of human fibroblasts expressing constitutively active (CA) RhoA, Cdc42 or Rac1. There was no marked effect of
any CA GTPase on cell adhesion to different extracellular matrix proteins. Cell spreading was CA Rho GTPase specific and independent
of the extracellular matrix proteins allowing adhesion. Mechanical properties were dramatically restricted by CA RhoA on bi-
and in tri-dimensional surroundings, were boosted by CA Rac1 on bi-dimensional surroundings only, and were not or marginally
affected by CA Cdc42. In conclusion, the action of Rho GTPases appears to depend on the task cells are performing.
Received 12 September 2005; received after revision 5 October 2005; accepted 1 November 2005 相似文献
67.
YunFei Bi J. Blanchard J. -F. Lambert Y. Millot P. P. Man ShuangQin Zeng Hong Nie DaDong Li MingFeng Li QingHe Yang XiaoXin Chen 《科学通报(英文版)》2010,55(23):2584-2588
In this paper, a new delaminated mesoporous material was prepared by swelling the lamellar phyllosilicate Magadiite using cetyltrimethylammonium bromide and tetrapropylammonium hydroxide solution, followed by delamination under the cavitation of ultrasonic treatment. Various characterization tools including XRD, N2 adsorption, NMR, IR, SEM and TEM were employed to observe its structure and morphology. XRD results show that the delaminated material has no long-range crystalline order. Fur-thermore, not only high surface area is obtained, but almost half of it is external surface. The observation for the morphology further reveals that it is made up of the random stacking of single or few layers. All these characters show that this delaminated mesoporous material meets the requirements for application as support in the hydrotreatment of heavy molecules. 相似文献
68.
Painter JN Anderson CA Nyholt DR Macgregor S Lin J Lee SH Lambert A Zhao ZZ Roseman F Guo Q Gordon SD Wallace L Henders AK Visscher PM Kraft P Martin NG Morris AP Treloar SA Kennedy SH Missmer SA Montgomery GW Zondervan KT 《Nature genetics》2011,43(1):51-54
Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10??, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10??, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10?3, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10?? (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10. 相似文献
69.
Jin Y Birlea SA Fain PR Ferrara TM Ben S Riccardi SL Cole JB Gowan K Holland PJ Bennett DC Luiten RM Wolkerstorfer A van der Veen JP Hartmann A Eichner S Schuler G van Geel N Lambert J Kemp EH Gawkrodger DJ Weetman AP Taïeb A Jouary T Ezzedine K Wallace MR McCormack WT Picardo M Leone G Overbeck A Silverberg NB Spritz RA 《Nature genetics》2012,44(6):676-680
We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration. 相似文献
70.
Lahortiga I De Keersmaecker K Van Vlierberghe P Graux C Cauwelier B Lambert F Mentens N Beverloo HB Pieters R Speleman F Odero MD Bauters M Froyen G Marynen P Vandenberghe P Wlodarska I Meijerink JP Cools J 《Nature genetics》2007,39(5):593-595
We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL. 相似文献