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181.
Chen Huang Xiaohua Geng Qinfei Ke Xiumei Mo Salem S. Al-Dey Mohamed El-Newehy 《自然科学进展(英文版)》2012,22(2):108-114
A novel type of composite vascular graft was developed via electrospinning in the present investigation.Collagen and chitosan were blended to form the inner and outer layer.Poly(1-lactide-co-caprolacto... 相似文献
182.
183.
RNAi-mediated gene silencing in non-human primates 总被引:2,自引:0,他引:2
Zimmermann TS Lee AC Akinc A Bramlage B Bumcrot D Fedoruk MN Harborth J Heyes JA Jeffs LB John M Judge AD Lam K McClintock K Nechev LV Palmer LR Racie T Röhl I Seiffert S Shanmugam S Sood V Soutschek J Toudjarska I Wheat AJ Yaworski E Zedalis W Koteliansky V Manoharan M Vornlocher HP MacLachlan I 《Nature》2006,441(7089):111-114
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs. 相似文献
184.
提出了可变频时钟写入方法和锁相环倍频时钟写入方法,给出了这两种写入法的读/写电路,并分析了其性能。结果证明,可变频时钟写入方法电路简单,刻写时钟周期短;锁相环倍频时钟写入过程较前者长,但其频率范围容易调整。两者均适合高密度小型温盘的时钟录写。 相似文献
185.
Inactivation of the apoptosis effector Apaf-1 in malignant melanoma 总被引:47,自引:0,他引:47
Soengas MS Capodieci P Polsky D Mora J Esteller M Opitz-Araya X McCombie R Herman JG Gerald WL Lazebnik YA Cordón-Cardó C Lowe SW 《Nature》2001,409(6817):207-211
Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type. 相似文献
186.
S. Ali Ghafari Oskoei Ghyslaine McClure Department of Civil Engineering Applied Mechanics McGill University Montréal Québec HA K Canada 《清华大学学报》2008,13(Z1):53-57
At present, high-speed computing capabilities and advanced nonlinear dynamic finite element procedures enable detailed dynamic analysis of cable structures. Although deterministic approaches require considerable analysis time and effort in relation to modeling, running, and data processing, they seem to be the only alternative to obtain high accuracy. Detailed dynamic analysis of cable roof networks is sophisticated and requires advanced modeling expertise. This paper presents a comparison between detailed nonlinear dynamic analysis and a simplified frequency domain approach to estimate the maximum probable response of weakly nonlinear cable roofs. The approach can be considered as alternative to detailed time-domain analysis in the preliminary design phase, or can be used to validate results obtained from more elaborated numerical models. The proposed method is illustrated with two examples of cable net roofs that were also analysed in the time domain. 相似文献
187.
肖人彬 《华中科技大学学报(自然科学版)》1994,(12)
阐述了人的建模思维机制。引入等价关系和划分作为问题粒度研究的基础,定义了逆商集,使之与商集一起,构成了对问题不同粒度的完整描述,并讨论了粒度的性质,借助拓扑分析,给出了问题可分解、可细化和粗化、细化等一系列定义,在问题簇和模型簇概念的基础上,提出了嵌套式建模(支持)作为面向复杂系统的建模支持方法论,具体给出了其实施步骤,这是一个人机交互的启发式过程,将嵌套式建模与传统式建模作了比较,此外还作了若干说明。 相似文献
188.
基于换热过程中的损失率能定量地反映该过程中流体的传热与流动的综合性能这一特性,借助换热过程的损失率方程,分析比较了几种流体工质在不同换热方式下的综合特性。比较结果表明,液体(如水)有远优于气体(如空气)的流动与传热的综合性能,且随着流体温度的升高其优势更为明显。同时表明分析法在定量评价换热工质性能的突出特点及工程上的应用价值。 相似文献
189.
采用球面刀在三坐标数控机床上加工具有凸曲面工位的零部件时,往往会导致几何形状误差,对此,运用点涉法原理,推导出在凸曲面上确定平头立铣刀五轴和三轴数控联动加工刀位轨迹的计算方法。 相似文献
190.
Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells 总被引:102,自引:0,他引:102
R L Williams D J Hilton S Pease T A Willson C L Stewart D P Gearing E F Wagner D Metcalf N A Nicola N M Gough 《Nature》1988,336(6200):684-687
Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice. 相似文献