全文获取类型
收费全文 | 16827篇 |
免费 | 38篇 |
国内免费 | 75篇 |
专业分类
系统科学 | 53篇 |
丛书文集 | 173篇 |
教育与普及 | 67篇 |
理论与方法论 | 49篇 |
现状及发展 | 7642篇 |
研究方法 | 659篇 |
综合类 | 8139篇 |
自然研究 | 158篇 |
出版年
2012年 | 196篇 |
2011年 | 334篇 |
2009年 | 99篇 |
2008年 | 261篇 |
2007年 | 287篇 |
2006年 | 264篇 |
2005年 | 281篇 |
2004年 | 323篇 |
2003年 | 288篇 |
2002年 | 280篇 |
2001年 | 466篇 |
2000年 | 491篇 |
1999年 | 337篇 |
1994年 | 304篇 |
1992年 | 268篇 |
1991年 | 223篇 |
1990年 | 278篇 |
1989年 | 252篇 |
1988年 | 260篇 |
1987年 | 282篇 |
1986年 | 290篇 |
1985年 | 338篇 |
1984年 | 233篇 |
1983年 | 257篇 |
1982年 | 212篇 |
1981年 | 204篇 |
1980年 | 245篇 |
1979年 | 508篇 |
1978年 | 434篇 |
1977年 | 390篇 |
1976年 | 314篇 |
1975年 | 386篇 |
1974年 | 474篇 |
1973年 | 422篇 |
1972年 | 431篇 |
1971年 | 562篇 |
1970年 | 608篇 |
1969年 | 531篇 |
1968年 | 532篇 |
1967年 | 459篇 |
1966年 | 408篇 |
1965年 | 294篇 |
1964年 | 128篇 |
1959年 | 166篇 |
1958年 | 322篇 |
1957年 | 253篇 |
1956年 | 202篇 |
1955年 | 200篇 |
1954年 | 193篇 |
1948年 | 167篇 |
排序方式: 共有10000条查询结果,搜索用时 977 毫秒
431.
Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. 总被引:53,自引:0,他引:53
D P Rich M P Anderson R J Gregory S H Cheng S Paul D M Jefferson J D McCann K W Klinger A E Smith M J Welsh 《Nature》1990,347(6291):358-363
The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease. 相似文献
432.
Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. 总被引:46,自引:0,他引:46
Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects. 相似文献
433.
Expression and characterization of the cystic fibrosis transmembrane conductance regulator. 总被引:36,自引:0,他引:36
R J Gregory S H Cheng D P Rich J Marshall S Paul K Hehir L Ostedgaard K W Klinger M J Welsh A E Smith 《Nature》1990,347(6291):382-386
Cystic fibrosis (CF) is a common lethal genetic disease that manifests itself in airway and other epithelial cells as defective chloride ion absorption and secretion, resulting at least in part from a defect in a cyclic AMP-regulated, outwardly-rectifying Cl- channel in the apical surface. The gene responsible for CF has been identified and predicted to encode a membrane protein termed the CF transmembrane conductance regulator (CFTR). Identification of a cryptic bacterial promoter within the CFTR coding sequence led us to construct a complementary DNA in a low-copy-number plasmid, thereby avoiding the deleterious effects of CFTR expression on Escherischia coli. We have used this cDNA to express CFTR in vitro and in vivo. Here we demonstrate that CFTR is a membrane-associated glycoprotein that can be phosporylated in vitro by cAMP-dependent protein kinase. Polyclonal and monoclonal antibodies directed against distinct domains of the protein immunoprecipitated recombinant CFTR as well as the endogenous CFTR in nonrecombinant T84 cells. Partial proteolysis fingerprinting showed that the recombinant and non-recombinant proteins are indistinguishable. These data, which establish several characteristics of the protein responsible for CF, will now enable CFTR function to be studied and will provide a basis for diagnosis and therapy. 相似文献
434.
435.
Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor 总被引:39,自引:0,他引:39
Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor. 相似文献
436.
Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins 总被引:59,自引:0,他引:59
A complementary DNA encoding the D100 polypeptide of rat brain dynamin--a force-producing, microtubule-activated nucleotide triphosphatase--has been cloned and sequenced. The predicted amino acid sequence includes a guanine nucleotide-binding domain that is homologous with those of a family of antiviral factors, inducible by interferon and known as Mx proteins, and with the product of the essential yeast vacuolar protein sorting gene VPS1. These relationships imply the existence of a new family of GTPases with physiological roles that may include microtubule-based motility and protein sorting. 相似文献
437.
438.
本文将文献[3]的引理1推广到s-单式环上,并用迭代技术给出文献[4]的定理2一个简易的证明,将若干有1环的交换性定理推广到s-单式环上。 相似文献
439.
探讨了溅射用铁电陶瓷靶(PZT,PLZT)的烧结工艺,并对其显微结构进行了分析。结果表明,采用新的烧结工艺(含保护措施),可以有效地抑制PbO的挥发,制备出组织结构及成分均匀、PbO含量正常、致密度较高、不变形的符合磁控溅射要求的铁电陶瓷烧结靶。 相似文献
440.
基于对时间序列实质的分析,提出了旨在减少序列的随机误差影响以及提高拟合精度的AR模型参数的积分求解法.重点讨论了AR(1)模型及AR(p)模型参数的积分求解法,并与最小二乘法在计算机上进行了仿真比较.结果表明,采用积分求解法所得的AR模型参数的估计精度比最小二乘法的高. 相似文献