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231.
Shaw C 《Population trends》2007,(128):8-23
This article considers the accuracy of the official national population projections made for the UK over the last fifty years The findings take account of the revision to population estimates following the 2001 Census and are largely similar to the findings of a previous review carried out after the 1991 Census. The total population has been projected reasonably accurately but this is largely a chance result of compensating errors in the assumptions of fertility, mortality and net migration. The largest differences between projected and actual populations are for the very young and the very old, while projections of the working age population have been comparatively accurate. Fertility and mortality errors have reduced in more recent projections, while migration errors have grown. However, this may simply reflect the volatility or stability of the respective time-series at the time the projections are made. Changes in estimates of the past and current size of the population (highlighted by the revisions made to population estimates following the 2001 Census) are also shown to play a part in explaining projection error. 相似文献
232.
Tarpey P Thomas S Sarvananthan N Mallya U Lisgo S Talbot CJ Roberts EO Awan M Surendran M McLean RJ Reinecke RD Langmann A Lindner S Koch M Jain S Woodruff G Gale RP Bastawrous A Degg C Droutsas K Asproudis I Zubcov AA Pieh C Veal CD Machado RD Backhouse OC Baumber L Constantinescu CS Brodsky MC Hunter DG Hertle RW Read RJ Edkins S O'Meara S Parker A Stevens C Teague J Wooster R Futreal PA Trembath RC Stratton MR Raymond FL Gottlob I 《Nature genetics》2006,38(11):1242-1244
Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability. 相似文献
233.
Vithana EN Morgan P Sundaresan P Ebenezer ND Tan DT Mohamed MD Anand S Khine KO Venkataraman D Yong VH Salto-Tellez M Venkatraman A Guo K Hemadevi B Srinivasan M Prajna V Khine M Casey JR Inglehearn CF Aung T 《Nature genetics》2006,38(7):755-757
Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay. 相似文献
234.
Chryssi Mytilineou Aikaterini Anastasopoulou George Christides Petros Bekas Chris J. Smith Konstantia N. Papadopoulou 《Journal of Natural History》2013,47(25-28):1645-1662
We report new species records and information related to meristic, morphometric, bathymetric and biological characteristics that increase our knowledge of the deep ichthyofauna of the Ionian Sea (E. Mediterranean). The material was collected with long lines from 300 to 800 m deep in the Eastern Ionian Sea in June and October 2010. The fish species Schedophilus ovalis (Cuvier, 1833) (Osteichthyes: Centrolophidae), Sudis hyalina Rafinesque, 1810 (Osteicthyes: Paralepididae), Brama brama (Bonnaterre, 1788) (Osteichthyes: Bramidae) and Trachipterus trachypterus (Gmelin, 1789) (Osteichthyes: Trachipteridae) were recorded for the first time in the Eastern Ionian Sea. The absence of these new or rare species from the ichthyofauna of the study area to date is probably related to the absence of adequate sampling and catching techniques, although environmental factors could also be involved. 相似文献
235.
Ludovic Dume′ e Aaron Thornton Kallista Sears Ju¨ rg Schu¨ tz Niall Finn Steven Spoljari Robert Shanks Chris Skourtis Mikel Duke Stephen Gray 《自然科学进展(英文版)》2012,22(6):673-683
In-situ thermal expansion tests on a series of carbon nanotube bucky-paper composites
were performed with direct heating within a synchrotron SAXS source. The impact of the samples
density and morphology as well as the chemistry and degree of decoration of the carbon nanotubes
on the scattering patterns were investigated and correlated to the materials macro-properties. The
results demonstrate that simple densification techniques, such as acetone dipping or gold electroless
deposition, could reduce greatly the displacements of the carbon nanotubes within the structure
and lead to more thermally stable material. 相似文献
236.
DT Jones N Jäger M Kool T Zichner B Hutter M Sultan YJ Cho TJ Pugh V Hovestadt AM Stütz T Rausch HJ Warnatz M Ryzhova S Bender D Sturm S Pleier H Cin E Pfaff L Sieber A Wittmann M Remke H Witt S Hutter T Tzaridis J Weischenfeldt B Raeder M Avci V Amstislavskiy M Zapatka UD Weber Q Wang B Lasitschka CC Bartholomae M Schmidt C von Kalle V Ast C Lawerenz J Eils R Kabbe V Benes P van Sluis J Koster R Volckmann D Shih MJ Betts RB Russell S Coco GP Tonini U Schüller V Hans N Graf YJ Kim C Monoranu 《Nature》2012,488(7409):100-105
Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients. 相似文献
237.
An integrated encyclopedia of DNA elements in the human genome 总被引:4,自引:0,他引:4
ENCODE Project Consortium BE Bernstein E Birney I Dunham ED Green C Gunter M Snyder 《Nature》2012,489(7414):57-74
238.
MC Scimia C Hurtado S Ray S Metzler K Wei J Wang CE Woods NH Purcell D Catalucci T Akasaka OF Bueno GP Vlasuk P Kaliman R Bodmer LH Smith E Ashley M Mercola JH Brown P Ruiz-Lozano 《Nature》2012,488(7411):394-398
Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy. 相似文献
239.
240.
Gehrig SM van der Poel C Sayer TA Schertzer JD Henstridge DC Church JE Lamon S Russell AP Davies KE Febbraio MA Lynch GS 《Nature》2012,484(7394):394-398
Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies. 相似文献