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271.
Molecular pathways driving disease-specific alterations of intestinal epithelial cells 总被引:1,自引:1,他引:0
Rocío López-Posadas Markus F. Neurath Imke Atreya 《Cellular and molecular life sciences : CMLS》2017,74(5):803-826
Due to the fact that chronic inflammation as well as tumorigenesis in the gut is crucially impacted by the fate of intestinal epithelial cells, our article provides a comprehensive overview of the composition, function, regulation and homeostasis of the gut epithelium. In particular, we focus on those aspects which were found to be altered in the context of inflammatory bowel diseases or colorectal cancer and also discuss potential molecular targets for a disease-specific therapeutic intervention. 相似文献
272.
Rocío Aguilar-Cuenca Alba Juanes-García Miguel Vicente-Manzanares 《Cellular and molecular life sciences : CMLS》2014,71(3):479-492
Mechanotransduction encompasses the role of mechanical forces in controlling cell behavior by activating signal transduction pathways. Most forces at a cellular level are caused by myosin II, which contracts and cross-links actin. Myosin II-dependent forces are transmitted through the actin cytoskeleton to molecular endpoints that promote specific cellular outcomes, e.g., cell proliferation, adhesion, or migration. For example, most adhesive and migratory phenomena are mechanically linked by a molecular clutch comprised of mechanosensitive scaffolds. Myosin II activation and mechanosensitive molecular mechanisms are finely tuned and spatiotemporally integrated to coordinate morphogenetic events during development. Mechanical events dependent on myosin II also participate in tumor cell proliferation, invasion, and metastatic dissemination. Specifically, tumor cells alter the mechanical properties of the microenvironment to create favorable conditions for proliferation and/or dissemination. These observations position myosin II-dependent force generation and mechanotransduction at the crossroads between normal development and cancer. 相似文献
273.
274.
Priscila A. Grohmann Ricardo S. Absalão Vera Maria Abud P. da Silva 《Journal of Natural History》2013,47(25-28):1865-1874
Project HABITATS was recently initiated in the Campos Basin (20.5–24° S), state of Rio de Janeiro, to assess biological impacts of petroleum exploration and exploitation on the continental shelf and slope of Brazil. Among species discovered in benthic samples from the area is the hydroid Monobrachium parasitum Mereschkowsky, 1877, occurring in an epibiotic association with the pelecypod mollusc Mendicula ferruginosa (Forbes, 1844): this is the first report of an association between the two species. Monobrachium parasitum has always been reported from cold waters, and is generally considered bipolar. This report records the occurrence of M. parasitum at lower latitudes, where they have seldom been collected: it is also the first account of this species from South America and the southwestern Atlantic. Moreover, the bathymetric distribution of M. parasitum is extended to a depth of 998 m. No previous records exist of hydroids from the Brazilian continental slope. 相似文献
275.
Barak T Kwan KY Louvi A Demirbilek V Saygı S Tüysüz B Choi M Boyacı H Doerschner K Zhu Y Kaymakçalan H Yılmaz S Bakırcıoğlu M Cağlayan AO Oztürk AK Yasuno K Brunken WJ Atalar E Yalçınkaya C Dinçer A Bronen RA Mane S Ozçelik T Lifton RP Sestan N Bilgüvar K Günel M 《Nature genetics》2011,43(6):590-594
The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations. 相似文献
276.
Stacey SN Sulem P Jonasdottir A Masson G Gudmundsson J Gudbjartsson DF Magnusson OT Gudjonsson SA Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Nexø BA Tjønneland A Overvad K Rudnai P Gurzau E Koppova K Hemminki K Corredera C Fuentelsaz V Grasa P Navarrete S Fuertes F García-Prats MD Sanambrosio E Panadero A De Juan A Garcia A Rivera F Planelles D Soriano V Requena C Aben KK van Rossum MM Cremers RG van Oort IM van Spronsen DJ Schalken JA Peters WH Helfand BT Donovan JL 《Nature genetics》2011,43(11):1098-1103
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27). 相似文献
277.
Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
278.
Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia 总被引:1,自引:0,他引:1
Zenatti PP Ribeiro D Li W Zuurbier L Silva MC Paganin M Tritapoe J Hixon JA Silveira AB Cardoso BA Sarmento LM Correia N Toribio ML Kobarg J Horstmann M Pieters R Brandalise SR Ferrando AA Meijerink JP Durum SK Yunes JA Barata JT 《Nature genetics》2011,43(10):932-939
Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL. 相似文献
279.
280.
Hashibe M McKay JD Curado MP Oliveira JC Koifman S Koifman R Zaridze D Shangina O Wünsch-Filho V Eluf-Neto J Levi JE Matos E Lagiou P Lagiou A Benhamou S Bouchardy C Szeszenia-Dabrowska N Menezes A Dall'Agnol MM Merletti F Richiardi L Fernandez L Lence J Talamini R Barzan L Mates D Mates IN Kjaerheim K Macfarlane GJ Macfarlane TV Simonato L Canova C Holcátová I Agudo A Castellsagué X Lowry R Janout V Kollarova H Conway DI McKinney PA Znaor A Fabianova E Bencko V Lissowska J Chabrier A Hung RJ 《Nature genetics》2008,40(6):707-709
Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology. 相似文献