全文获取类型
收费全文 | 19171篇 |
免费 | 539篇 |
国内免费 | 865篇 |
专业分类
系统科学 | 959篇 |
丛书文集 | 443篇 |
教育与普及 | 455篇 |
理论与方法论 | 94篇 |
现状及发展 | 2049篇 |
研究方法 | 225篇 |
综合类 | 16337篇 |
自然研究 | 13篇 |
出版年
2023年 | 157篇 |
2022年 | 260篇 |
2021年 | 268篇 |
2020年 | 216篇 |
2019年 | 126篇 |
2018年 | 167篇 |
2017年 | 197篇 |
2016年 | 229篇 |
2015年 | 431篇 |
2014年 | 615篇 |
2013年 | 671篇 |
2012年 | 810篇 |
2011年 | 967篇 |
2010年 | 913篇 |
2009年 | 1056篇 |
2008年 | 1162篇 |
2007年 | 1175篇 |
2006年 | 933篇 |
2005年 | 885篇 |
2004年 | 731篇 |
2003年 | 576篇 |
2002年 | 655篇 |
2001年 | 742篇 |
2000年 | 632篇 |
1999年 | 633篇 |
1998年 | 347篇 |
1997年 | 331篇 |
1996年 | 344篇 |
1995年 | 304篇 |
1994年 | 292篇 |
1993年 | 215篇 |
1992年 | 280篇 |
1991年 | 255篇 |
1990年 | 223篇 |
1989年 | 202篇 |
1988年 | 169篇 |
1987年 | 142篇 |
1986年 | 93篇 |
1985年 | 107篇 |
1979年 | 146篇 |
1978年 | 134篇 |
1977年 | 107篇 |
1974年 | 98篇 |
1973年 | 103篇 |
1972年 | 90篇 |
1971年 | 111篇 |
1970年 | 100篇 |
1969年 | 96篇 |
1968年 | 95篇 |
1967年 | 87篇 |
排序方式: 共有10000条查询结果,搜索用时 218 毫秒
901.
Y Y Toyoshima S J Kron E M McNally K R Niebling C Toyoshima J A Spudich 《Nature》1987,328(6130):536-539
The rotating crossbridge model for muscle contraction proposes that force is produced by a change in angle of the crossbridge between the overlapping thick and thin filaments. Myosin, the major component of the thick filament, is comprised of two heavy chains and two pairs of light chains. Together they form two globular heads, which give rise to the crossbridge in muscle, and a coiled-coil rod, which forms the shaft of the thick filament. The isolated head fragment, subfragment-1 (S1), contains the ATPase and actin-binding activities of myosin (Fig. 1). Although S1 seems to have the requisite enzymatic activity, direct evidence that S1 is sufficient to drive actin movement has been lacking. It has long been recognized that in vitro movement assays are an important approach for identifying the elements in muscle responsible for force generation. Hynes et al. showed that beads coated with heavy meromyosin (HMM), a soluble proteolytic fragment of myosin consisting of a part of the rod and the two heads, can move on Nitella actin filaments. Using the myosin-coated surface assay of Kron and Spudich, Harada et al. showed that single-headed myosin filaments bound to glass support movement of actin at nearly the same speed as intact myosin filaments. These studies show that the terminal portion of the rod and the two-headed nature of myosin are not required for movement. To restrict the region responsible for movement further, we have modified the myosin-coated surface assay by replacing the glass surface with a nitrocellulose film. Here we report that myosin filaments, soluble myosin, HMM or S1, when bound to a nitrocellulose film, support actin sliding movement (Fig. 2). That S1 is sufficient to cause sliding movement of actin filaments in vitro gives strong support to models of contraction that place the site of active movement in muscle within the myosin head. 相似文献
902.
Expression and functional characterization of artificial mutants of interleukin-2 receptor 总被引:1,自引:0,他引:1
The physiological proliferation of T lymphocytes (T cells) requires interaction between the humoral growth factor, interleukin 2 (IL-2) and its cell-surface receptor. Studies of IL-2 binding to the IL-2 receptor (IL-2R) on T cells have revealed that there are two distinct species of IL-2R, one with high and one with low affinity. Isolation and characterization of cDNA for the human IL-2R made it possible to deduce the complete primary sequence (251 residues) of the receptor protein. However, expression of IL-2R alone is not sufficient for either growth signal transduction or high-affinity site formation: another lymphocyte-specific molecule called converter seems to be required for the biological activity of IL-2R. We found that the converter did not form a stable complex with IL-2R unless the receptor bound the ligand (the 'affinity conversion' model). To discover which are the functionally important parts of the human IL-2R we have constructed artificial mutant cDNAs encoding the receptor. The mutant receptors produced from them had deletions or substitutions in the cytoplasmic region (13 residues), the transmembrane region (19 residues) or the carboxy-terminal portion of the extracellular region (219 residues). All were active in growth signal transduction, efficient internalization and high-affinity site formation in two mouse T-cell lines, suggesting that the extracellular region of IL-2R and the converter may be responsible for growth signal transduction. 相似文献
903.
B Sredni R R Caspi A Klein Y Kalechman Y Danziger M Ben Ya'akov T Tamari F Shalit M Albeck 《Nature》1987,330(6144):173-176
There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O'-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression. 相似文献
904.
HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product 总被引:2,自引:0,他引:2
B Guy M P Kieny Y Riviere C Le Peuch K Dott M Girard L Montagnier J P Lecocq 《Nature》1987,330(6145):266-269
Apart from the retroviral gag, pol and env the HIV genome contains the F (3' orf) gene which encodes a polypeptide of 206 amino acids which is myristylated at the N-terminal and whose function is unknown. We have expressed the F gene in Escherichia coli and from a recombinant vaccinia virus, VVTGfHIV. The F-protein produced in VVTGfHIV-infected mammalian cells is myristilated, and is phosphorylated by protein kinase C at a residue close to the N-terminus like pp60-src (ref. 5). Purified bacterial F-protein also shows the GTPase, autophosphorylation and GTP-binding activities reported for the ras gene product. Furthermore, we show that expression of F in a CD4+ cell line down-regulates the CD4(T4) antigen. These results suggest that F is important in the pathophysiology of AIDS (acquired immune deficiency syndrome). 相似文献
905.
Kinetics of smooth and skeletal muscle activation by laser pulse photolysis of caged inositol 1,4,5-trisphosphate 总被引:1,自引:0,他引:1
Inositol 1,4,5-trisphosphate (InsP3) can stimulate skinned smooth and skeletal muscle to contract by initiating Ca2+ release from the sarcoplasmic reticulum. Whether this process is an integral component of the in vivo muscle activation mechanism was tested by releasing InsP3 rapidly within skinned muscle fibers of rabbit main pulmonary artery and frog semitendinosus. InsP3 was liberated on laser pulse photolysis of a photolabile but biologically inactive precursor of InsP3 termed caged InsP3. Caged InsP3 is a mixture of compounds in which InsP3 is esterified with 1(2-nitrophenyl)diazoethane (probably at the P4- or P5-position). Photochemical release of InsP3 induced a full contraction in both muscles at physiological free Mg2+ concentrations, but only in the smooth muscle were the InsP3 concentration (0.5 microM) and the activation rate compatible with the in vivo physiological response. Endogenous InsP3-specific phosphatase activity was present in smooth muscle and had about 35-fold greater activity than that in the skeletal-muscle preparation. Caged InsP3 was not susceptible to phosphatases in either preparation. 相似文献
906.
We compared the effects ofAlzheimer's peptide (Abeta1-42), a,-antichymotrypsin (ACT) and an ACT/Abeta1-42 mixture on human glioma DK-MG cells. The solution of Abeta (5 microM) formed by 2-h incubation at room temperature induced tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels by 55 and 45%, respectively, and increased gelatinase B activity by 67%, while exposure of cells to the ACT/Abeta1-42 mixture (1:10 molar ratio ACT: Abeta1-42) under the same experimental conditions showed no effect on IL-6 levels or gelatinase B activity, but strongly induced TNF-alpha (by 190%), compared to the controls. Stimulation of the cells with Abeta1-42 alone, but not with ACT, increased by about 20% low-density lipoprotein (LDL) uptake and mRNA levels for LDL receptor and HMG-CoA reductase, while the ACT/Abeta1-42 mixture significantly increased LDL uptake (by 50%), up-regulated mRNA levels for LDL receptor and HMG-CoA reductase by 48 and 63%, respectively, and increased lipid accumulation by about 20-fold. These data suggest a possible new role for Abeta in Alzheimer's disease through its interaction with the inflammatory reactant, ACT. 相似文献
907.
Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex 总被引:36,自引:0,他引:36
Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits. 相似文献
908.
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
909.
甘薯新品种"渝苏30"选育研究 总被引:2,自引:1,他引:1
介绍了甘薯新品种“渝苏30”的生产力和主要经济性状的鉴定结果。在1997年至1998年重庆市甘薯新品种区域试验中,鲜薯产量35.80t/hm^2,藤叶产量24.90t/hm^2,生物鲜产量60.70t/hm^2,生物干产量12.50t/hm^2,分别比对照“南薯88”增产9.31%,14.43%,11.36%和0.73%m,其薯干产量9.03t/hm^2,比对照“南薯88”减产3.94%,它在生产上产量表现更好,该品种萌芽性好,结薯较早,大中薯率85%以上,薯块烘干率25.38%,出粉率11.87%,氨基酸含量0.71%,“渝苏30”抗旱性强,抗黑斑病,贮藏性好。 相似文献
910.
设计了一种水泥生产线自动化监控系统.并论证了系统的组成、工作原理、硬件设计和软件设计,该系统经过在府谷水泥厂投入使用以后,效果令人满意,具有较高的推广价值. 相似文献