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101.
A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. 总被引:81,自引:0,他引:81
N A Thornberry H G Bull J R Calaycay K T Chapman A D Howard M J Kostura D K Miller S M Molineaux J R Weidner J Aunins 《Nature》1992,356(6372):768-774
Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target. 相似文献
102.
Antigen presentation enhanced by the alternatively spliced invariant chain gene product p41. 总被引:5,自引:0,他引:5
During biosynthesis, class II molecules of the major histocompatibility complex are associated with a nonpolymorphic protein called invariant chain, Ii, which facilitates folding of class II molecules and their exit from the endoplasmic reticulum, interferes with their association with peptide and directs their post-Golgi transport (refs 7-9). If Ii blocks class II loading with endogenous antigens in the endoplasmic reticulum and/or directs class II molecules to the exogenous antigen-loading compartment, then the co-expression of Ii should enhance the ability of class II molecules to present exogenous antigens to T cells. But data supporting a role for Ii in class II-restricted antigen presentation are controversial. Here we show that Ii can facilitate exogenous antigen presentation for a subset of antigens. Although all known functions of Ii have been ascribed to the principal form of Ii, p31, we find that in most cases antigen presentation is facilitated only by the alternatively spliced, minor form of Ii, p41. 相似文献
103.
Female mites of the species Pyemotes tritici inject an extremely potent venom into their insect prey that causes muscle-contraction and paralysis. These mites are able to paralyse insects 150,000 times their size and their venom is effective in a broad range of insect species. A toxin (TxP-I) associated with the mite venom apparatus causes immediate muscle-contractive paralysis when injected into insects but not mice. In this report, we describe the cloning, sequencing and expression of a complementary DNA (Tox-34) encoding TxP-I. Insect cells infected with a recombinant baculovirus (vEV-Tox34) expressing Tox-34 secrete three polypeptides related to TxP-I which cause paralysis on injection. Larvae infected with vEV-Tox34 become paralysed during infection, thus reflecting the potential application of this toxin gene in insect biocontrol methods. The toxin gene expression system will also allow further exploration of the neurophysiological basis of its insect-specific effects. 相似文献
104.
Peripheral deletion of self-reactive B cells 总被引:27,自引:0,他引:27
B LYMPHOCYTES are key participants in the immune response because of their specificity, their ability to take up and present antigens to T cells, and their capacity to differentiate into antibody-secreting cells. To limit reactivity to self antigens, autospecific B cells can be functionally inactivated or deleted. Developing B cells that react with membrane antigens expressed in the bone marrow are deleted from the peripheral lymphocyte pool. It is important to ascertain the fate of B cells that recognize membrane autoantigens expressed exclusively on peripheral tissues because B cells in the peripheral lymphoid organs are phenotypically and functionally distinct from bone-marrow B cells. Here we show that in immunoglobulin-transgenic mice, B cells specific for major histocompatibility complex class I antigen can be deleted if they encounter membrane-bound antigen at a post-bone-marrow stage of development. This deletion may be necessary to prevent organ-specific autoimmunity. 相似文献
105.
106.
S Kitao A Shimamoto M Goto R W Miller W A Smithson N M Lindor Y Furuichi 《Nature genetics》1999,22(1):82-84
Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired somatic mosaicism. The gene(s) responsible for RTS remains unknown. The genes responsible for Werner and Bloom syndromes (WRN and BLM, respectively) have been identified as homologues of Escherichia coli RecQ, which encodes a DNA helicase that unwinds double-stranded DNA into single-stranded DNAs. Other eukaryotic homologues thus far identified are human RECQL, Saccharomyces cerevisiae SGS1 and Schizosaccharomyces pombe rqh1. We recently cloned two new human helicase genes, RECQL4 at 8q24.3 and RECQL5 at 17q25, which encode members of the RecQ helicase family. Here, we report that three RTS patients carried two types of compound heterozygous mutations in RECQL4. The fact that the mutated alleles were inherited from the parents in one affected family and were not found in ethnically matched controls suggests that mutation of RECQL4 at human chromosome 8q24.3 is responsible for at least some cases of RTS. 相似文献
107.
Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. 总被引:34,自引:0,他引:34
M McClelland K E Sanderson J Spieth S W Clifton P Latreille L Courtney S Porwollik J Ali M Dante F Du S Hou D Layman S Leonard C Nguyen K Scott A Holmes N Grewal E Mulvaney E Ryan H Sun L Florea W Miller T Stoneking M Nhan R Waterston R K Wilson 《Nature》2001,413(6858):852-856
Salmonella enterica subspecies I, serovar Typhimurium (S. typhimurium), is a leading cause of human gastroenteritis, and is used as a mouse model of human typhoid fever. The incidence of non-typhoid salmonellosis is increasing worldwide, causing millions of infections and many deaths in the human population each year. Here we sequenced the 4,857-kilobase (kb) chromosome and 94-kb virulence plasmid of S. typhimurium strain LT2. The distribution of close homologues of S. typhimurium LT2 genes in eight related enterobacteria was determined using previously completed genomes of three related bacteria, sample sequencing of both S. enterica serovar Paratyphi A (S. paratyphi A) and Klebsiella pneumoniae, and hybridization of three unsequenced genomes to a microarray of S. typhimurium LT2 genes. Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12. The 352 gene homologues of S. typhimurium LT2 confined to subspecies I of S. enterica-containing most mammalian and bird pathogens-are useful for studies of epidemiology, host specificity and pathogenesis. Most of these homologues were previously unknown, and 50 may be exported to the periplasm or outer membrane, rendering them accessible as therapeutic or vaccine targets. 相似文献
108.
用CASI遥感数据估计横跨美国俄勒冈州针叶林叶面积指数 总被引:7,自引:0,他引:7
使用三类模型技术,对小型航空光谱制图成像仪(CASI)数据被用作估计针叶林叶面积指数(LAI)的潜力进行研究。三类技术为:单变量回归,多变量回归和植被指数(VI)基础的LAI估计模型。沿横跨美国俄勒冈州的各植被区选择四个研究立地,分别测定和收集LAI数据和CASI图像数据。CASI数据经校准后,研究其与LAI测定值的关系。结果说明二种成像方式的CASI数据对于LAI估计具有相似的效率。与其它两种技术比,逐步回归方法导致较高的LAI预测精度。在单变量回归和VI基础法中使用NDVI,比起其它形式的CASI数据能产生较好的效果。 相似文献
109.
Boyd PW Law CS Wong CS Nojiri Y Tsuda A Levasseur M Takeda S Rivkin R Harrison PJ Strzepek R Gower J McKay M Abraham E Arychuk M Barwell-Clarke J Crawford W Crawford D Hale M Harada K Johnson K Kiyosawa H Kudo I Marchetti A Miller W Needoba J Nishioka J Ogawa H Page J Robert M Saito H Sastri A Sherry N Soutar T Sutherland N Taira Y Whitney F Wong SK Yoshimura T 《Nature》2004,428(6982):549-553
Iron supply has a key role in stimulating phytoplankton blooms in high-nitrate low-chlorophyll oceanic waters. However, the fate of the carbon fixed by these blooms, and how efficiently it is exported into the ocean's interior, remains largely unknown. Here we report on the decline and fate of an iron-stimulated diatom bloom in the Gulf of Alaska. The bloom terminated on day 18, following the depletion of iron and then silicic acid, after which mixed-layer particulate organic carbon (POC) concentrations declined over six days. Increased particulate silica export via sinking diatoms was recorded in sediment traps at depths between 50 and 125 m from day 21, yet increased POC export was not evident until day 24. Only a small proportion of the mixed-layer POC was intercepted by the traps, with more than half of the mixed-layer POC deficit attributable to bacterial remineralization and mesozooplankton grazing. The depletion of silicic acid and the inefficient transfer of iron-increased POC below the permanent thermocline have major implications both for the biogeochemical interpretation of times of greater iron supply in the geological past, and also for proposed geo-engineering schemes to increase oceanic carbon sequestration. 相似文献
110.
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day CL Kaufmann DE Kiepiela P Brown JA Moodley ES Reddy S Mackey EW Miller JD Leslie AJ DePierres C Mncube Z Duraiswamy J Zhu B Eichbaum Q Altfeld M Wherry EJ Coovadia HM Goulder PJ Klenerman P Ahmed R Freeman GJ Walker BD 《Nature》2006,443(7109):350-354
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. 相似文献