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排序方式: 共有174条查询结果,搜索用时 31 毫秒
91.
Résumé Les ovaires de souris C3B6F1, génotypeW
xWv développent des adénomes tubulaires à l'âge de 7 mois. Dans l'essai du tread wheel l'activité spontanée de ces animaux était plus petite que celle des contrôles. 相似文献
92.
Torgerson DG Ampleford EJ Chiu GY Gauderman WJ Gignoux CR Graves PE Himes BE Levin AM Mathias RA Hancock DB Baurley JW Eng C Stern DA Celedón JC Rafaels N Capurso D Conti DV Roth LA Soto-Quiros M Togias A Li X Myers RA Romieu I Van Den Berg DJ Hu D Hansel NN Hernandez RD Israel E Salam MT Galanter J Avila PC Avila L Rodriquez-Santana JR Chapela R Rodriguez-Cintron W Diette GB Adkinson NF Abel RA Ross KD Shi M Faruque MU Dunston GM Watson HR Mantese VJ Ezurum SC Liang L Ruczinski I Ford JG 《Nature genetics》2011,43(9):887-892
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma. 相似文献
93.
Sarno S Mazzorana M Traynor R Ruzzene M Cozza G Pagano MA Meggio F Zagotto G Battistutta R Pinna LA 《Cellular and molecular life sciences : CMLS》2012,69(3):449-460
8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of
protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter
as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as
“denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC50 > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases
that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC50 values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural
features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit
of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68
and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved
water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to
the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A
by dNBC. 相似文献
94.
RA Scott V Lagou RP Welch E Wheeler ME Montasser J Luan R Mägi RJ Strawbridge E Rehnberg S Gustafsson S Kanoni LJ Rasmussen-Torvik L Yengo C Lecoeur D Shungin S Sanna C Sidore PC Johnson JW Jukema T Johnson A Mahajan N Verweij G Thorleifsson JJ Hottenga S Shah AV Smith B Sennblad C Gieger P Salo M Perola NJ Timpson DM Evans BS Pourcain Y Wu JS Andrews J Hui LF Bielak W Zhao M Horikoshi P Navarro A Isaacs JR O'Connell K Stirrups V Vitart C Hayward T Esko E Mihailov RM Fraser T Fall BF Voight 《Nature genetics》2012,44(9):991-1005
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. 相似文献
95.
Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids 总被引:1,自引:0,他引:1
Rademakers R Baker M Nicholson AM Rutherford NJ Finch N Soto-Ortolaza A Lash J Wider C Wojtas A DeJesus-Hernandez M Adamson J Kouri N Sundal C Shuster EA Aasly J MacKenzie J Roeber S Kretzschmar HA Boeve BF Knopman DS Petersen RC Cairns NJ Ghetti B Spina S Garbern J Tselis AC Uitti R Das P Van Gerpen JA Meschia JF Levy S Broderick DF Graff-Radford N Ross OA Miller BB Swerdlow RH Dickson DW Wszolek ZK 《Nature genetics》2012,44(2):200-205
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis. 相似文献
96.
Christina M. Dobson Samuel J. Hempel Stephanie H. Stalnaker Ryan Stuart Lance Wells 《Cellular and molecular life sciences : CMLS》2013,70(16):2849-2857
Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway. 相似文献
97.
Craig Guyer Christopher Murray Henry L. Bart Brian I. Crother Ryan E. Chabarria Mark A. Bailey 《Journal of Natural History》2020,54(1-4):15-41
ABSTRACT Recent data from the mitochondrial genome reveal six lineages of Gulf Coast Waterdogs traditionally classified as Necturus beyeri. Here, we use patterns of colour and body size, along with previously published data, to reveal a large, heavily spotted phenotype with an unstriped larva possessing numerous white spots; we re-describe N. beyeri to correspond to this phenotype. We also reveal a small, weakly spotted phenotype possessing an unstriped larva lacking numerous white spots. This phenotype characterises the Apalachicola and Escambia lineages, which current evidence suggests are paraphyletic. We reject taxonomies that place these two lineages in N. lodingi because the type specimen of this species appears to be a melanistic member of N. beyeri. Therefore, we describe the Apalachicola and Escambia lineages as independent new species. http://ww.zoobank.org/urn:lsid:zoobank.org:act:C8508CCB-F54F-4DC8-B61D-56966A3F1CC8 http://www.zoobank.org/urn:lsid:zoobank.org:act:F044B2CC-55F0-4FFA-A312-9CAD9E73CD69 相似文献
98.
Systemic Practice and Action Research - Experienced system dynamicists commonly conceptualise causal relationships and feedback loops using Causal Loop Diagrams (CLDs). In adhering to best... 相似文献
99.
Sarita D. Lee Andy A. Shen Junhyung Park Ryan J. Harrigan Nicole A. Hoff Anne W. Rimoin Frederic Paik Schoenberg 《Journal of forecasting》2022,41(1):201-210
Point process models, such as Hawkes and recursive models, have recently been shown to offer improved accuracy over more traditional compartmental models for the purposes of modeling and forecasting the spread of disease epidemics. To explicitly test the performance of these two models in a real-world and ongoing epidemic, we compared the fit of Hawkes and recursive models to outbreak data on Ebola virus disease (EVD) in the Democratic Republic of the Congo in 2018–2020. The models were estimated, and the forecasts were produced, time-stamped, and stored in real time, so that their prospective value can be assessed and to guard against potential overfitting. The fit of the two models was similar, with both models resulting in much smaller errors in the beginning and waning phases of the epidemic and with slightly smaller error sizes on average for the Hawkes model compared with the recursive model. Our results suggest that both Hawkes and recursive point process models can be used in near real time during the course of an epidemic to help predict future cases and inform management and mitigation strategies. 相似文献
100.
Animals' sound-producing organs often act as an integrated whole--particular vocal structure are not directly associated with the creation of discrete syllables. But here we show that the 'chuck' of the 'whine-chuck' mating call of the túngara frog, Physalaemus pustulosus, is caused by a fibrous mass attached to the vocal folds; the chuck is eliminated by removal of this structure, although the frog still tries to produce the sound. Sexual selection affects the acoustic complexity of the frog's call, so evolution may have shaped this unusual vocalization, which is akin to the two-voiced song of songbirds. 相似文献