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451.
RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease 总被引:19,自引:0,他引:19
Bucciarelli LG Wendt T Rong L Lalla E Hofmann MA Goova MT Taguchi A Yan SF Yan SD Stern DM Schmidt AM 《Cellular and molecular life sciences : CMLS》2002,59(7):1117-1128
Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered. 相似文献
452.
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus 总被引:21,自引:0,他引:21
Altfeld M Allen TM Yu XG Johnston MN Agrawal D Korber BT Montefiori DC O'Connor DH Davis BT Lee PK Maier EL Harlow J Goulder PJ Brander C Rosenberg ES Walker BD 《Nature》2002,420(6914):434-439
Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development. 相似文献
453.
Wabnitz H Bittner L de Castro AR Döhrmann R Gürtler P Laarmann T Laasch W Schulz J Swiderski A von Haeften K Möller T Faatz B Fateev A Feldhaus J Gerth C Hahn U Saldin E Schneidmiller E Sytchev K Tiedtke K Treusch R Yurkov M 《Nature》2002,420(6915):482-485
Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion. 相似文献
454.
The coordination of signals from different pathways is important for cell fate specification during animal development. Here, we define a novel mode of crosstalk between the epidermal growth factor receptor/Ras/mitogen-activated protein kinase cascade and the LIN-12/Notch pathway during Caenorhabditis elegans vulval development. Six vulval precursor cells (VPCs) are initially equivalent but adopt different fates as a result of an inductive signal mediated by the Ras pathway and a lateral signal mediated by the LIN-12/Notch pathway. One consequence of activating Ras is a reduction of LIN-12 protein in P6.p (ref. 2), the VPC believed to be the source of the lateral signal. Here we identify a 'downregulation targeting signal' (DTS) in the LIN-12 intracellular domain, which encompasses a di-leucine-containing endocytic sorting motif. The DTS seems to be required for internalization of LIN-12, and on Ras activation it might mediate altered endocytic routing of LIN-12, leading to downregulation. We also show that if LIN-12 is stabilized in P6.p, lateral signalling is compromised, indicating that LIN-12 downregulation is important in the appropriate specification of cell fates in vivo. 相似文献
455.
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs 总被引:6,自引:0,他引:6
Okazaki Y Furuno M Kasukawa T Adachi J Bono H Kondo S Nikaido I Osato N Saito R Suzuki H Yamanaka I Kiyosawa H Yagi K Tomaru Y Hasegawa Y Nogami A Schönbach C Gojobori T Baldarelli R Hill DP Bult C Hume DA Quackenbush J Schriml LM Kanapin A Matsuda H Batalov S Beisel KW Blake JA Bradt D Brusic V Chothia C Corbani LE Cousins S Dalla E Dragani TA Fletcher CF Forrest A Frazer KS Gaasterland T Gariboldi M Gissi C Godzik A Gough J Grimmond S Gustincich S Hirokawa N Jackson IJ Jarvis ED Kanai A 《Nature》2002,420(6915):563-573
456.
457.
Gardner MJ Shallom SJ Carlton JM Salzberg SL Nene V Shoaibi A Ciecko A Lynn J Rizzo M Weaver B Jarrahi B Brenner M Parvizi B Tallon L Moazzez A Granger D Fujii C Hansen C Pederson J Feldblyum T Peterson J Suh B Angiuoli S Pertea M Allen J Selengut J White O Cummings LM Smith HO Adams MD Venter JC Carucci DJ Hoffman SL Fraser CM 《Nature》2002,419(6906):531-534
The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome. 相似文献
458.
Mutations of the BRAF gene in human cancer 总被引:2,自引:0,他引:2
Davies H Bignell GR Cox C Stephens P Edkins S Clegg S Teague J Woffendin H Garnett MJ Bottomley W Davis N Dicks E Ewing R Floyd Y Gray K Hall S Hawes R Hughes J Kosmidou V Menzies A Mould C Parker A Stevens C Watt S Hooper S Wilson R Jayatilake H Gusterson BA Cooper C Shipley J Hargrave D Pritchard-Jones K Maitland N Chenevix-Trench G Riggins GJ Bigner DD Palmieri G Cossu A Flanagan A Nicholson A Ho JW Leung SY Yuen ST Weber BL Seigler HF Darrow TL Paterson H Marais R Marshall CJ Wooster R 《Nature》2002,417(6892):949-954
Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma. 相似文献
459.
460.