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排序方式: 共有302条查询结果,搜索用时 31 毫秒
111.
Lorenzen ED Nogués-Bravo D Orlando L Weinstock J Binladen J Marske KA Ugan A Borregaard MK Gilbert MT Nielsen R Ho SY Goebel T Graf KE Byers D Stenderup JT Rasmussen M Campos PF Leonard JA Koepfli KP Froese D Zazula G Stafford TW Aaris-Sørensen K Batra P Haywood AM Singarayer JS Valdes PJ Boeskorov G Burns JA Davydov SP Haile J Jenkins DL Kosintsev P Kuznetsova T Lai X Martin LD McDonald HG Mol D Meldgaard M Munch K Stephan E Sablin M Sommer RS Sipko T Scott E Suchard MA Tikhonov A Willerslev R 《Nature》2011,479(7373):359-364
Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change. 相似文献
112.
113.
Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma 总被引:26,自引:0,他引:26
N Sarvetnick J Shizuru D Liggitt L Martin B McIntyre A Gregory T Parslow T Stewart 《Nature》1990,346(6287):844-847
Interferon-gamma (IFN-gamma) is produced during the response to infection and participates in immunostimulatory events. We have previously reported the induction of diabetes in transgenic mice (ins-IFN-gamma) in which the expression of the lymphokine IFN-gamma is directed by the insulin promoter. This diabetes is a result of the progressive destruction of pancreatic islets that occurs with the influx of inflammatory cells. Here we demonstrate that this islet cell loss is mediated by lymphocytes, that engrafted histocompatible islets are destroyed, and that lymphocytes from the transgenic mice are cytotoxic to normal islets in vitro. These results indicate that the pancreatic expression of IFN-gamma can result in a loss of tolerance to normal islets, consistent with its role as an inducer of costimulatory activity, which is essential for lymphocyte activation during an immune response. 相似文献
114.
The missing memristor found 总被引:17,自引:0,他引:17
Anyone who ever took an electronics laboratory class will be familiar with the fundamental passive circuit elements: the resistor, the capacitor and the inductor. However, in 1971 Leon Chua reasoned from symmetry arguments that there should be a fourth fundamental element, which he called a memristor (short for memory resistor). Although he showed that such an element has many interesting and valuable circuit properties, until now no one has presented either a useful physical model or an example of a memristor. Here we show, using a simple analytical example, that memristance arises naturally in nanoscale systems in which solid-state electronic and ionic transport are coupled under an external bias voltage. These results serve as the foundation for understanding a wide range of hysteretic current-voltage behaviour observed in many nanoscale electronic devices that involve the motion of charged atomic or molecular species, in particular certain titanium dioxide cross-point switches. 相似文献
115.
Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids. 相似文献
116.
117.
Thorgeirsson TE Geller F Sulem P Rafnar T Wiste A Magnusson KP Manolescu A Thorleifsson G Stefansson H Ingason A Stacey SN Bergthorsson JT Thorlacius S Gudmundsson J Jonsson T Jakobsdottir M Saemundsdottir J Olafsdottir O Gudmundsson LJ Bjornsdottir G Kristjansson K Skuladottir H Isaksson HJ Gudbjartsson T Jones GT Mueller T Gottsäter A Flex A Aben KK de Vegt F Mulders PF Isla D Vidal MJ Asin L Saez B Murillo L Blondal T Kolbeinsson H Stefansson JG Hansdottir I Runarsdottir V Pola R Lindblad B 《Nature》2008,452(7187):638-642
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases. 相似文献
118.
Carpten JD Faber AL Horn C Donoho GP Briggs SL Robbins CM Hostetter G Boguslawski S Moses TY Savage S Uhlik M Lin A Du J Qian YW Zeckner DJ Tucker-Kellogg G Touchman J Patel K Mousses S Bittner M Schevitz R Lai MH Blanchard KL Thomas JE 《Nature》2007,448(7152):439-444
Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development. 相似文献
119.
MicroRNA silencing through RISC recruitment of eIF6 总被引:1,自引:0,他引:1
Chendrimada TP Finn KJ Ji X Baillat D Gregory RI Liebhaber SA Pasquinelli AE Shiekhattar R 《Nature》2007,447(7146):823-828
120.
Scally A Dutheil JY Hillier LW Jordan GE Goodhead I Herrero J Hobolth A Lappalainen T Mailund T Marques-Bonet T McCarthy S Montgomery SH Schwalie PC Tang YA Ward MC Xue Y Yngvadottir B Alkan C Andersen LN Ayub Q Ball EV Beal K Bradley BJ Chen Y Clee CM Fitzgerald S Graves TA Gu Y Heath P Heger A Karakoc E Kolb-Kokocinski A Laird GK Lunter G Meader S Mort M Mullikin JC Munch K O'Connor TD Phillips AD Prado-Martinez J Rogers AS Sajjadian S Schmidt D Shaw K Simpson JT Stenson PD Turner DJ 《Nature》2012,483(7388):169-175
Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution. 相似文献