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991.
992.
993.
为了解决在入射平面SV波和Rayleigh波作用下地下圆形衬砌洞室的动应力集中问题,利用文献[5]的级数解,分析了衬砌刚度、入射波长、入射角度诸因素对动应力集中系数(DSCF)的影响。数值结果表明:(1)衬砌刚度对DSCF有重要影响,柔性衬砌情况DSCF最小,刚性衬砌情况的最大;环向与轴向DSCF最大可分别达到32.31与16.12;(2)入射频率和入射角度对DSCF也有很大影响。 相似文献
994.
The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling. Impaired Ca(2+) uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene delivery maintained the protein abundance of SERCA2a and markedly improved cardiac function in mice with heart failure. This effect was comparable to SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay. Transgene-mediated SUMO1 overexpression rescued cardiac dysfunction induced by pressure overload concomitantly with increased SERCA2a function. By contrast, downregulation of SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced deterioration of cardiac function and was accompanied by decreased SERCA2a function. However, knockdown of SERCA2a resulted in severe contractile dysfunction both in vitro and in vivo, which was not rescued by overexpression of SUMO1. Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure. 相似文献
995.
Breitbach CJ Burke J Jonker D Stephenson J Haas AR Chow LQ Nieva J Hwang TH Moon A Patt R Pelusio A Le Boeuf F Burns J Evgin L De Silva N Cvancic S Robertson T Je JE Lee YS Parato K Diallo JS Fenster A Daneshmand M Bell JC Kirn DH 《Nature》2011,477(7362):99-102
The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans. 相似文献
996.
Low molecular weight (LMW) organic acids are important and ubiquitous chemical constituents in the atmosphere. A comprehensive
study of the chemical composition of precipitation was carried out from June 2007 to June 2008 at a rural site in Anshun,
in the west of Guizhou Province, China. During this period, 118 rainwater samples were collected and the main LMW carboxylic
acids were determined using ion chromatography. The average pH of rainwater was 4.89 which is a typical acidic value. The
most abundant carboxylic acids were formic acid (volume weight mean concentration: 8.77 μmol L−1) and acetic acid (6.90 μmol L−1), followed by oxalic acid (2.05 μmol L−1). The seasonal variation of concentrations and wet deposition fluxes of organic acids indicated that direct vegetation emissions
were the main sources of the organic acids. Highest concentrations were observed in winter and were ascribed to the low winter
rainfall and the contribution of other air pollution sources northeast of the study area. The ratio of formic and acetic acids
in the precipitation ([F/A]
T
) was proposed as an indicator of pollution source. This suggested that the pollution resulted from direct emissions from
natural or anthropogenic sources. Comparison with acid precipitation in other urban and rural areas in Guizhou showed that
there was a decreasing contribution of LMW organic acids to free acidity and all anions in rainwater from urban to remote
rural areas. Consequently, it is necessary to control emissions of organic acids to reduce the frequency of acid rain, especially
in rural and remote areas. 相似文献
997.
The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons. 相似文献
998.
The elevational gradient present in mountainous areas provides the most powerful natural experimental system available to clarify the ecological and evolutionary responses of living organisms to geophysical influences. In this study, we explored the elevational patterns of plant species and functional diversity and the effects of area, mid-domain effect, climatic variables and net primary productivity on the observed diversity patterns along the ridge of the Baekdudaegan Mountains, South Korea. Rapoport’s elevational rule was also evaluated by examining the relationship between elevational range size of plant species and elevation. A total of 802 plant species from 97 families and 342 genera were found in 1100 plots along a 200–-1900-m elevational gradient along the ridge. The elevational patterns of plant species diversity along the ridge of the Baekdudaegan depicted distinctly hump-shaped patterns, whereas the functional diversity decreased monotonically with elevation. The mid-domain effect was the most powerful explanatory variable for species diversity patterns. However, climatic variables were better predictors for functional diversity. Moreover, Rapoport’s elevational rule was not supported. Our study suggests that different elevational patterns may be observed among different diversity measurements even in the same taxon and that there may be fundamental differences in the mechanisms underlying these diversity patterns. 相似文献
999.
Synthesis of supported Au-Ag bimetallic has attracted much attention since we found for the first time that Au and Ag had synergistic effect on CO oxidation and preferential CO oxidation in rich hydrogen.In this work,the formation of Au-Ag alloy nanoparticles supported on silica gel by galvanic replacement reaction has been investigated.We applied various characterizations including X-ray diffraction(XRD),transmission electronic microscopy(TEM),ultraviolet-visible spectroscopy(UV-vis),X-ray absorption spectroscopy(XAS) to characterize the formation process of Au-Ag alloy.Although the average particle sizes of the Au-Ag alloy nanoparticles obtained by the galvanic replacement reaction are relatively large comparing with that of loading Au first,the catalytic activity of the catalyst in preferential CO oxidation is almost the same.This result manifested that the particle size effect of Au-Ag nanoparticles was not as tremendous as that of monometallic gold.The formation of Au-Ag alloy made it less sensitive to the particle size. 相似文献
1000.
Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor 总被引:1,自引:0,他引:1
Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development. 相似文献