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301.
Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification 总被引:8,自引:0,他引:8
Rutsch F Ruf N Vaingankar S Toliat MR Suk A Höhne W Schauer G Lehmann M Roscioli T Schnabel D Epplen JT Knisely A Superti-Furga A McGill J Filippone M Sinaiko AR Vallance H Hinrichs B Smith W Ferre M Terkeltaub R Nürnberg P 《Nature genetics》2003,34(4):379-381
Idiopathic infantile arterial calcification (IIAC; OMIM 208000) is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. We analyzed affected individuals from 11 unrelated kindreds and found that IIAC was associated with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification. 相似文献
302.
Gibbons RJ Pellagatti A Garrick D Wood WG Malik N Ayyub H Langford C Boultwood J Wainscoat JS Higgs DR 《Nature genetics》2003,34(4):446-449
Inherited mutations of specific genes have elucidated the normal roles of the proteins they encode by relating specific mutations to particular phenotypes. But many potentially informative mutations in such genes are lethal early in development. Consequently, inherited mutations may not reflect all the functional roles of such proteins. Acquired, somatic defects should reflect a wider spectrum of mutations because they are not prone to negative selection in development. It has been difficult to identify such mutations so far, but microarray analysis provides a new opportunity to do so. Using this approach, we have shown that in individuals with myelodysplasia associated with alpha-thalassemia (ATMDS), somatic mutations of the gene encoding the chromatin remodeling factor ATRX cause an unexpectedly severe hematological phenotype compared with the wide spectrum of inherited mutations affecting this gene. These findings cast new light on this pleiotropic cofactor, which appears to be an essential component rather than a mere facilitator of globin gene expression. 相似文献
303.
Dodé C Levilliers J Dupont JM De Paepe A Le Dû N Soussi-Yanicostas N Coimbra RS Delmaghani S Compain-Nouaille S Baverel F Pêcheux C Le Tessier D Cruaud C Delpech M Speleman F Vermeulen S Amalfitano A Bachelot Y Bouchard P Cabrol S Carel JC Delemarre-van de Waal H Goulet-Salmon B Kottler ML Richard O Sanchez-Franco F Saura R Young J Petit C Hardelin JP 《Nature genetics》2003,33(4):463-465
We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males. 相似文献
304.
Yamada K Andrews C Chan WM McKeown CA Magli A de Berardinis T Loewenstein A Lazar M O'Keefe M Letson R London A Ruttum M Matsumoto N Saito N Morris L Del Monte M Johnson RH Uyama E Houtman WA de Vries B Carlow TJ Hart BL Krawiecki N Shoffner J Vogel MC Katowitz J Goldstein SM Levin AV Sener EC Ozturk BT Akarsu AN Brodsky MC Hanisch F Cruse RP Zubcov AA Robb RM Roggenkäemper P Gottlob I Kowal L Battu R Traboulsi EI Franceschini P Newlin A Demer JL Engle EC 《Nature genetics》2003,35(4):318-321
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis. 相似文献
305.
306.
G. G. Tedeschi G. Sprovieri Paola Del Prete 《Cellular and molecular life sciences : CMLS》1978,34(5):596-598
Summary The evolution of cocci and diphtheroids taking origin from cell-wall-deficient forms seems not to be related to a particular state of illness, but to be the consequence of a generalized crypto-infection. 相似文献
307.
Karnoub AE Dash AB Vo AP Sullivan A Brooks MW Bell GW Richardson AL Polyak K Tubo R Weinberg RA 《Nature》2007,449(7162):557-563
Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells. 相似文献
308.