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61.
O. Nilsson 《Cellular and molecular life sciences : CMLS》1964,20(12):679-680
Zusammenfassung Nor-Adrenalin (NA) verschwindet nach einer Reserpininjektion im Uterus des Kaninchens langsamer als in anderen Organen: nach 12 h noch Nachweis von Aminen in den vasomotorischen Uterusnerven, nicht aber zum Beispiel in derGl. submandibularis. Tendenz zu gleicher Reaktion zeigt der Uterus des Meerschweinchens, nicht aber der Ratte, der Maus oder des Hamsters. Es wird der Schluss gezogen, dass verschiedene sympathische Nervenendigungen gleicher Aufgabe variierende Grundeigenschaften zeigen.
This study was aided by grant NB 02854-04 from the United States Public Health Service. 相似文献
This study was aided by grant NB 02854-04 from the United States Public Health Service. 相似文献
62.
V Lotteau L Teyton A Peleraux T Nilsson L Karlsson S L Schmid V Quaranta P A Peterson 《Nature》1990,348(6302):600-605
Three structural motifs in the invariant chain (li) control the intracellular transport of class II major histocompatibility complex molecules. An endoplasmic reticulum retention signal in the full-length li suggests a role for li in the alpha-beta heterodimer assembly. Another signal motif directs a truncated li, alone or associated with individual class II chains, to a degradation compartment by a pathway circumventing the Golgi. When this truncated li binds alpha-beta dimers, a third signal dominates, directing the complex by way of the Golgi to vesicles in the cell periphery, which may represent a subcompartment of recycling endosomes. 相似文献
63.
A recurrent mutation in PALB2 in Finnish cancer families 总被引:1,自引:0,他引:1
Erkko H Xia B Nikkilä J Schleutker J Syrjäkoski K Mannermaa A Kallioniemi A Pylkäs K Karppinen SM Rapakko K Miron A Sheng Q Li G Mattila H Bell DW Haber DA Grip M Reiman M Jukkola-Vuorinen A Mustonen A Kere J Aaltonen LA Kosma VM Kataja V Soini Y Drapkin RI Livingston DM Winqvist R 《Nature》2007,446(7133):316-319
BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer. Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified. The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity. Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development. 相似文献
64.
Apoptosis is a vital component in the evolutionarily conserved host defense system. Apoptosis is the guardian of tissue integrity
by removing unfit and injured cells without evoking inflammation. However, apoptosis seems to be a double-edged sword since
during low-level chronic stress, such as in aging, increased resistance to apoptosis can lead to the survival of functionally
deficient, post-mitotic cells with damaged housekeeping functions. Senescent cells are remarkably resistant to apoptosis,
and several studies indicate that host defense mechanisms can enhance anti-apoptotic signaling, which subsequently induces
a senescent, pro-inflammatory phenotype during the aging process. At the molecular level, age-related resistance to apoptosis
involves (1) functional deficiency in p53 network, (2) increased activity in the NF-κB-IAP/JNK axis, and (3) changes in molecular
chaperones, microRNAs, and epigenetic regulation. We will discuss the molecular basis of age-related resistance to apoptosis
and emphasize that increased resistance could enhance the aging process. 相似文献
65.
Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease 总被引:1,自引:1,他引:0
66.
Kote-Jarai Z Olama AA Giles GG Severi G Schleutker J Weischer M Campa D Riboli E Key T Gronberg H Hunter DJ Kraft P Thun MJ Ingles S Chanock S Albanes D Hayes RB Neal DE Hamdy FC Donovan JL Pharoah P Schumacher F Henderson BE Stanford JL Ostrander EA Sorensen KD Dörk T Andriole G Dickinson JL Cybulski C Lubinski J Spurdle A Clements JA Chambers S Aitken J Gardiner RA Thibodeau SN Schaid D John EM Maier C Vogel W Cooney KA Park JY Cannon-Albright L Brenner H Habuchi T Zhang HW Lu YJ Kaneva R 《Nature genetics》2011,43(8):785-791
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ~25% of the familial risk in this disease, have now been identified. 相似文献
67.
Yasuda K Miyake K Horikawa Y Hara K Osawa H Furuta H Hirota Y Mori H Jonsson A Sato Y Yamagata K Hinokio Y Wang HY Tanahashi T Nakamura N Oka Y Iwasaki N Iwamoto Y Yamada Y Seino Y Maegawa H Kashiwagi A Takeda J Maeda E Shin HD Cho YM Park KS Lee HK Ng MC Ma RC So WY Chan JC Lyssenko V Tuomi T Nilsson P Groop L Kamatani N Sekine A Nakamura Y Yamamoto K Yoshida T Tokunaga K Itakura M Makino H Nanjo K Kadowaki T Kasuga M 《Nature genetics》2008,40(9):1092-1097
We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries. 相似文献
68.
Fagerholm R Hofstetter B Tommiska J Aaltonen K Vrtel R Syrjäkoski K Kallioniemi A Kilpivaara O Mannermaa A Kosma VM Uusitupa M Eskelinen M Kataja V Aittomäki K von Smitten K Heikkilä P Lukas J Holli K Bartkova J Blomqvist C Bartek J Nevanlinna H 《Nature genetics》2008,40(7):844-853
NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1(*)2, rs1800566(T), NM_000903.2:c.558C>T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P = 0.002, N = 1,005; P = 0.005, N = 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P = 7.52 x 10(-6)) and in p53-aberrant tumors (P = 6.15 x 10(-5)). Survival after metastasis was reduced among NQO1(*)2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1(*)2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53-independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest that the NQO1 genotype is a prognostic and predictive marker for breast cancer. 相似文献
69.
Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer
Stacey SN Manolescu A Sulem P Thorlacius S Gudjonsson SA Jonsson GF Jakobsdottir M Bergthorsson JT Gudmundsson J Aben KK Strobbe LJ Swinkels DW van Engelenburg KC Henderson BE Kolonel LN Le Marchand L Millastre E Andres R Saez B Lambea J Godino J Polo E Tres A Picelli S Rantala J Margolin S Jonsson T Sigurdsson H Jonsdottir T Hrafnkelsson J Johannsson J Sveinsson T Myrdal G Grimsson HN Sveinsdottir SG Alexiusdottir K Saemundsdottir J Sigurdsson A Kostic J Gudmundsson L Kristjansson K Masson G 《Nature genetics》2008,40(6):703-706
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer. 相似文献
70.
Lindström S Vachon CM Li J Varghese J Thompson D Warren R Brown J Leyland J Audley T Wareham NJ Loos RJ Paterson AD Rommens J Waggott D Martin LJ Scott CG Pankratz VS Hankinson SE Hazra A Hunter DJ Hopper JL Southey MC Chanock SJ Silva Idos S Liu J Eriksson L Couch FJ Stone J Apicella C Czene K Kraft P Hall P Easton DF Boyd NF Tamimi RM 《Nature genetics》2011,43(3):185-187
High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer. 相似文献