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131.
A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer 总被引:28,自引:0,他引:28
Hunter DJ Kraft P Jacobs KB Cox DG Yeager M Hankinson SE Wacholder S Wang Z Welch R Hutchinson A Wang J Yu K Chatterjee N Orr N Willett WC Colditz GA Ziegler RG Berg CD Buys SS McCarty CA Feigelson HS Calle EE Thun MJ Hayes RB Tucker M Gerhard DS Fraumeni JF Hoover RN Thomas G Chanock SJ 《Nature genetics》2007,39(7):870-874
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci. 相似文献
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DR.J.P.Semwal 《天津科技大学学报》2004,19(Z1)
INTRODUCTION
India is among one of the ten most industrialized nations in the world. Increase in population has raised the urbar industrial, transport and agriculture demands which are major reasons for the degradation of the environmel condition. For India besides land and soil degradation, deforestation, low accessibility of water, ,industrial pollution and urban congestion are the major environmental issues of priority. The industries that generate huge quantities of waste are thermal power station, Iron and Steel Plants, Sugar, Paper and Fertilizer Industries. 相似文献
134.
Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism 总被引:2,自引:0,他引:2
Dessaud E Yang LL Hill K Cox B Ulloa F Ribeiro A Mynett A Novitch BG Briscoe J 《Nature》2007,450(7170):717-720
Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression. 相似文献
135.
This report is a comparative study of the hyobranchial skeleton of the three species in the family Cyptobranchidae and four species of the family Hynobiidae, all of which are figured. Anatomical differences between the cryptobranchids and their relationship to hynobiids are noted and discussed. Reference is made to a relationship that may exist between these families and other salamander families, particularly the possible relationship of the Hynobiidae to the super families Ambystomatoidea or possibly Plethodontoidea. 相似文献
136.
Cox A Dunning AM Garcia-Closas M Balasubramanian S Reed MW Pooley KA Scollen S Baynes C Ponder BA Chanock S Lissowska J Brinton L Peplonska B Southey MC Hopper JL McCredie MR Giles GG Fletcher O Johnson N dos Santos Silva I Gibson L Bojesen SE Nordestgaard BG Axelsson CK Torres D Hamann U Justenhoven C Brauch H Chang-Claude J Kropp S Risch A Wang-Gohrke S Schürmann P Bogdanova N Dörk T Fagerholm R Aaltonen K Blomqvist C Nevanlinna H Seal S Renwick A Stratton MR Rahman N Sangrajrang S Hughes D 《Nature genetics》2007,39(3):352-358
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. 相似文献
137.
Eeles RA Kote-Jarai Z Giles GG Olama AA Guy M Jugurnauth SK Mulholland S Leongamornlert DA Edwards SM Morrison J Field HI Southey MC Severi G Donovan JL Hamdy FC Dearnaley DP Muir KR Smith C Bagnato M Ardern-Jones AT Hall AL O'Brien LT Gehr-Swain BN Wilkinson RA Cox A Lewis S Brown PM Jhavar SG Tymrakiewicz M Lophatananon A Bryant SL;UK Genetic Prostate Cancer Study Collaborators;British Association of Urological Surgeons' Section of Oncology;UK ProtecT Study Collaborators Horwich A Huddart RA 《Nature genetics》2008,40(3):316-321
Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at =60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 x 10(-8) to P = 8.7 x 10(-29)). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3. 相似文献
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139.
Zusammenfassung Der Stoffwechsel des3H-Thymidins in Blut-Leukozyten wurde während langfristiger Inkubation studiert. Die Bedingungen waren dieselben, die gewöhnlich for Chromosomenpräparate angewendet werden. So gelang es, menschliche Leukocyten während 72 Stunden mit H3-markiertem Thymidin zu inkubieren, ohne dass das markierte Thymidin durch die Leukozyt-Thymidin-Phosphorylase zerstört wurde.
This work was supported by research grant No. AM 14529 from the U.S. Public Health Service. D.M. is a Trainee in Genetics (HE 05307) and R.P.C. is a Career Scientist of the Health Research Council of the City of New York. 相似文献
This work was supported by research grant No. AM 14529 from the U.S. Public Health Service. D.M. is a Trainee in Genetics (HE 05307) and R.P.C. is a Career Scientist of the Health Research Council of the City of New York. 相似文献
140.