全文获取类型
收费全文 | 1088篇 |
免费 | 43篇 |
国内免费 | 36篇 |
专业分类
系统科学 | 20篇 |
丛书文集 | 2篇 |
教育与普及 | 3篇 |
理论与方法论 | 12篇 |
现状及发展 | 337篇 |
研究方法 | 134篇 |
综合类 | 631篇 |
自然研究 | 28篇 |
出版年
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 15篇 |
2018年 | 21篇 |
2017年 | 18篇 |
2016年 | 19篇 |
2015年 | 19篇 |
2014年 | 27篇 |
2013年 | 31篇 |
2012年 | 76篇 |
2011年 | 101篇 |
2010年 | 40篇 |
2009年 | 33篇 |
2008年 | 61篇 |
2007年 | 70篇 |
2006年 | 60篇 |
2005年 | 75篇 |
2004年 | 43篇 |
2003年 | 66篇 |
2002年 | 60篇 |
2001年 | 43篇 |
2000年 | 43篇 |
1999年 | 23篇 |
1996年 | 4篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 9篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 9篇 |
1974年 | 5篇 |
1973年 | 9篇 |
1972年 | 3篇 |
1971年 | 9篇 |
1970年 | 9篇 |
1969年 | 7篇 |
1968年 | 5篇 |
1967年 | 7篇 |
1966年 | 5篇 |
1965年 | 7篇 |
排序方式: 共有1167条查询结果,搜索用时 46 毫秒
181.
Herpes simplex virus 2 (HSV-2) infection causes significant morbidity and is an important cofactor for the transmission of HIV infection. A microbicide to prevent sexual transmission of HSV-2 would contribute substantially to controlling the spread of HIV and other infections. Because RNA interference (RNAi) provides effective antiviral defence in plants and other organisms, several studies have focused on harnessing RNAi to inhibit viral infection. Here we show that vaginal instillation of small interfering RNAs (siRNAs) targeting HSV-2 protects mice from lethal infection. siRNAs mixed with lipid are efficiently taken up by epithelial and lamina propria cells and silence gene expression in the mouse vagina and ectocervix for at least nine days. Intravaginal application of siRNAs targeting the HSV-2 UL27 and UL29 genes (which encode an envelope glycoprotein and a DNA binding protein, respectively) was well tolerated, did not induce interferon-responsive genes or cause inflammation, and protected mice when administered before and/or after lethal HSV-2 challenge. These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission. 相似文献
182.
183.
Zody MC Garber M Sharpe T Young SK Rowen L O'Neill K Whittaker CA Kamal M Chang JL Cuomo CA Dewar K FitzGerald MG Kodira CD Madan A Qin S Yang X Abbasi N Abouelleil A Arachchi HM Baradarani L Birditt B Bloom S Bloom T Borowsky ML Burke J Butler J Cook A DeArellano K DeCaprio D Dorris L Dors M Eichler EE Engels R Fahey J Fleetwood P Friedman C Gearin G Hall JL Hensley G Johnson E Jones C Kamat A Kaur A Locke DP Madan A Munson G Jaffe DB Lui A Macdonald P Mauceli E Naylor JW Nesbitt R Nicol R 《Nature》2006,440(7084):671-675
Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome. 相似文献
184.
Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 out of every 1,000 births. Mouse and frog models for these birth defects have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling might control neurulation by promoting the convergence of neural progenitors to the midline. Here we show a novel role for PCP signalling during neurulation in zebrafish. We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anteroposterior axis. This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium. Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs. Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension. These results reveal a function for PCP signalling in coupling cell division and morphogenesis at neurulation and indicate a previously unrecognized mechanism that might underlie NTDs. 相似文献
185.
The sensing of reactive oxygen species is essential for cellular responses to oxidative stress. The sensing of peroxides is typically mediated by redox-active cysteines in sensors such as the bacterial OxyR, OhrR, and Hsp33 proteins. Bacillus subtilis PerR is the prototype for a widespread family of metal-dependent peroxide sensors that regulate inducible peroxide-defence genes. Here we show that PerR senses peroxides by metal-catalysed oxidation. PerR contains two metal-binding sites: a structural Zn2+ site and a regulatory divalent metal ion site that preferentially binds Fe2+ or Mn2+ (ref. 5). Protein oxidation, catalysed by a bound ferrous ion, leads to the rapid and direct incorporation of one oxygen atom into histidine 37 (H37) or H91, two of the residues that coordinate the bound Fe2+. This mechanism accounts for the ability of PerR to sense low levels of hydrogen peroxide in vivo. The reduction of hydrogen peroxide by metal ions to generate highly reactive hydroxyl radicals underlies the genotoxic effects of peroxides, and has been shown to contribute to enzyme inactivation, but has not previously been shown to provide a regulatory mechanism for peroxide sensing. 相似文献
186.
Lee JW Beebe K Nangle LA Jang J Longo-Guess CM Cook SA Davisson MT Sundberg JP Schimmel P Ackerman SL 《Nature》2006,443(7107):50-55
Misfolded proteins are associated with several pathological conditions including neurodegeneration. Although some of these abnormally folded proteins result from mutations in genes encoding disease-associated proteins (for example, repeat-expansion diseases), more general mechanisms that lead to misfolded proteins in neurons remain largely unknown. Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons. These accumulations are accompanied by upregulation of cytoplasmic protein chaperones and by induction of the unfolded protein response. We report that the mouse sticky mutation, which causes cerebellar Purkinje cell loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA synthetase gene that compromises the proofreading activity of this enzyme during aminoacylation of tRNAs. These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration. 相似文献
187.
Metallic transport in polyaniline 总被引:2,自引:0,他引:2
Despite nearly three decades of materials development, the transport properties in the 'metallic state' of the so-called conducting polymers are still not typical of conventional metals. The hallmark of metallic resistivity--a monotonic decrease in resistivity with temperature--has not been obtained at temperatures over the full range below room temperature; and a frequency dependent conductivity, sigma(omega), typical of metals has also not been observed. In contrast, the low-temperature behaviour of 'metallic' polymers has, in all previous cases, exhibited an increase in resistivity as temperature is further decreased, as a result of disorder-induced localization of the charge carriers. This disorder-induced localization also changes the infrared response such that sigma(omega) deviates from the prediction of Drude theory. Here we report classic metallic transport data obtained from truly metallic polymers. With polyaniline samples prepared using self-stabilized dispersion polymerization, we find that for samples having room-temperature conductivities in excess of 1,000 S cm(-1), the resistivity decreases monotonically as the temperature is lowered down to 5 K, and that the infrared spectra are characteristic of the conventional Drude model even at the lowest frequencies measured. 相似文献
188.
189.
Xiaoyu Wang Yan Li Guang Wang Andrea Mnsterberg Manli Chuai KaHo Kenneth Lee Lijing Wang Xuesong Yang 《科学通报(英文版)》2014,59(7):616-624
Gene transfection is an indispensable approach for studying gene function since it provides important information on gain- and/or loss-of-function. Chick embryos are also extensively employed for studying bio- logical function since they are easily accessible and can be maintained alive after manipulation. The combination of both techniques presents a powerful approach to under- standing how genes regulate embryo development. Fur- thermore, combining these approaches with tissue transplant techniques make even more attractive for elu- cidate gene function. Electroporation, employing parallelly fashioned electrodes, has been widely used in chick embryos. However, experimenters have been frustrated by unsuccessfully transfection in some embryonic tissue of interest because the electrodes were improperly positioned.We presently demonstrated the different patterns of orga- nizing and positioning the electrodes, in combination with tissue transplantation, to efficiently and specifically trans- fect the chick embryonic head, trunk neural tube, heart tube, somites and neural crest cells with the GFP reporter gene. 相似文献
190.
S. Naddaf Dezfuli Zhigang Huan J.M.C. Mol M.A. Lee flang Jiang Chang Jie Zhou 《自然科学进展(英文版)》2014,24(5):531-538
The human body is a buffered environment where p H is effectively maintained. HEPES is a biological buffer often used to mimic the buffering activity of the body in in vitro studies on the degradation behavior of magnesium. However, the influence of HEPES on the degradation behavior of magnesium in the DMEM pseudo-physiological solution has not yet been determined. The research aimed at elucidating the degradation mechanisms of magnesium in DMEM with and without HEPES. The morphologies and compositions of surface layers formed during in vitro degradation tests for 15–3600 s were characterized. The effect of HEPES on the electrochemical behavior and corrosion tendency was determined by performing electrochemical tests. HEPES indeed retained the local p H, leading to intense intergranular/interparticle corrosion of magnesium made from powder and an increased degradation rate. This was attributed to an interconnected network of cracks formed at the original powder particle boundaries and grain boundaries in the surface layer, which provided pathways for the corrosive medium to interact continuously with the internal surfaces and promoted further dissolution. Surface analysis revealed significantly reduced amounts of precipitated calcium phosphates due to the buffering activity of HEPES so that magnesium became less well protected in the buffered environment. 相似文献