全文获取类型
收费全文 | 547篇 |
免费 | 0篇 |
专业分类
丛书文集 | 2篇 |
教育与普及 | 4篇 |
理论与方法论 | 1篇 |
现状及发展 | 44篇 |
研究方法 | 112篇 |
综合类 | 384篇 |
出版年
2012年 | 46篇 |
2011年 | 49篇 |
2010年 | 11篇 |
2009年 | 2篇 |
2008年 | 43篇 |
2007年 | 43篇 |
2006年 | 53篇 |
2005年 | 22篇 |
2004年 | 39篇 |
2003年 | 45篇 |
2002年 | 35篇 |
2001年 | 25篇 |
2000年 | 50篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1971年 | 5篇 |
1970年 | 12篇 |
1959年 | 5篇 |
1958年 | 7篇 |
1957年 | 6篇 |
1956年 | 3篇 |
1955年 | 3篇 |
1954年 | 5篇 |
1948年 | 6篇 |
排序方式: 共有547条查询结果,搜索用时 15 毫秒
511.
Munroe RJ Bergstrom RA Zheng QY Libby B Smith R John SW Schimenti KJ Browning VL Schimenti JC 《Nature genetics》2000,24(3):318-321
The drive to characterize functions of human genes on a global scale has stimulated interest in large-scale generation of mouse mutants. Conventional germ-cell mutagenesis with N-ethyl-N-nitrosourea (ENU) is compromised by an inability to monitor mutation efficiency, strain and interlocus variation in mutation induction, and extensive husbandry requirements. To overcome these obstacles and develop new methods for generating mouse mutants, we devised protocols to generate germline chimaeric mice from embryonic stem (ES) cells heavily mutagenized with ethylmethanesulphonate (EMS). Germline chimaeras were derived from cultures that underwent a mutation rate of up to 1 in 1,200 at the Hprt locus (encoding hypoxanthine guanine phosphoribosyl transferase). The spectrum of mutations induced by EMS and the frameshift mutagen ICR191 was consistent with that observed in other mammalian cells. Chimaeras derived from ES cells treated with EMS transmitted mutations affecting several processes, including limb development, hair growth, hearing and gametogenesis. This technology affords several advantages over traditional mutagenesis, including the ability to conduct shortened breeding schemes and to screen for mutant phenotypes directly in ES cells or their differentiated derivatives. 相似文献
512.
Regulation of transcription factor function by phosphorylation 总被引:1,自引:1,他引:0
513.
514.
IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23 总被引:22,自引:0,他引:22
Gharavi AG Yan Y Scolari F Schena FP Frasca GM Ghiggeri GM Cooper K Amoroso A Viola BF Battini G Caridi G Canova C Farhi A Subramanian V Nelson-Williams C Woodford S Julian BA Wyatt RJ Lifton RP 《Nature genetics》2000,26(3):354-357
End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene. 相似文献
515.
Kitov PI Sadowska JM Mulvey G Armstrong GD Ling H Pannu NS Read RJ Bundle DR 《Nature》2000,403(6770):669-672
The diseases caused by Shiga and cholera toxins account for the loss of millions of lives each year. Both belong to the clinically significant subset of bacterial AB5 toxins consisting of an enzymatically active A subunit that gains entry to susceptible mammalian cells after oligosaccharide recognition by the B5 homopentamer. Therapies might target the obligatory oligosaccharide-toxin recognition event, but the low intrinsic affinity of carbohydrate-protein interactions hampers the development of low-molecular-weight inhibitors. The toxins circumvent low affinity by binding simultaneously to five or more cell-surface carbohydrates. Here we demonstrate the use of the crystal structure of the B5 subunit of Escherichia coli O157:H7 Shiga-like toxin I (SLT-I) in complex with an analogue of its carbohydrate receptor to design an oligovalent, water-soluble carbohydrate ligand (named STARFISH), with subnanomolar inhibitory activity. The in vitro inhibitory activity is 1-10-million-fold higher than that of univalent ligands and is by far the highest molar activity of any inhibitor yet reported for Shiga-like toxins I and II. Crystallography of the STARFISH/Shiga-like toxin I complex explains this activity. Two trisaccharide receptors at the tips of each of five spacer arms simultaneously engage all five B subunits of two toxin molecules. 相似文献
516.
Simple rules yield complex food webs 总被引:42,自引:0,他引:42
Several of the most ambitious theories in ecology describe food webs that document the structure of strong and weak trophic links that is responsible for ecological dynamics among diverse assemblages of species. Early mechanism-based theory asserted that food webs have little omnivory and several properties that are independent of species richness. This theory was overturned by empirical studies that found food webs to be much more complex, but these studies did not provide mechanistic explanations for the complexity. Here we show that a remarkably simple model fills this scientific void by successfully predicting key structural properties of the most complex and comprehensive food webs in the primary literature. These properties include the fractions of species at top, intermediate and basal trophic levels, the means and variabilities of generality, vulnerability and food-chain length, and the degrees of cannibalism, omnivory, looping and trophic similarity. Using only two empirical parameters, species number and connectance, our 'niche model' extends the existing 'cascade model and improves its fit ten-fold by constraining species to consume a contiguous sequence of prey in a one-dimensional trophic niche. 相似文献
517.
Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia 总被引:19,自引:0,他引:19
Page NM Woods RJ Gardiner SM Lomthaisong K Gladwell RT Butlin DJ Manyonda IT Lowry PJ 《Nature》2000,405(6788):797-800
Pre-eclampsia is a principal cause of maternal morbidity and mortality, affecting 5-10% of first pregnancies worldwide. Manifestations include increased blood pressure, proteinuria, coagulopathy and peripheral and cerebral oedema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates the disease. Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB) of other mammalian species. In female rats, concentrations of NKB several-fold above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations of NKB were grossly elevated in pregnancy-induced hypertension and pre-eclampsia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. 相似文献
518.
Digital selection and analogue amplification coexist in a cortex-inspired silicon circuit 总被引:2,自引:0,他引:2
Digital circuits such as the flip-flop use feedback to achieve multistability and nonlinearity to restore signals to logical levels, for example 0 and 1. Analogue feedback circuits are generally designed to operate linearly, so that signals are over a range, and the response is unique. By contrast, the response of cortical circuits to sensory stimulation can be both multistable and graded. We propose that the neocortex combines digital selection of an active set of neurons with analogue response by dynamically varying the positive feedback inherent in its recurrent connections. Strong positive feedback causes differential instabilities that drive the selection of a set of active neurons under the constraints embedded in the synaptic weights. Once selected, the active neurons generate weaker, stable feedback that provides analogue amplification of the input. Here we present our model of cortical processing as an electronic circuit that emulates this hybrid operation, and so is able to perform computations that are similar to stimulus selection, gain modulation and spatiotemporal pattern generation in the neocortex. 相似文献
519.
Effect of aquaculture on world fish supplies 总被引:81,自引:0,他引:81
Naylor RL Goldburg RJ Primavera JH Kautsky N Beveridge MC Clay J Folke C Lubchenco J Mooney H Troell M 《Nature》2000,405(6790):1017-1024
Global production of farmed fish and shellfish has more than doubled in the past 15 years. Many people believe that such growth relieves pressure on ocean fisheries, but the opposite is true for some types of aquaculture. Farming carnivorous species requires large inputs of wild fish for feed. Some aquaculture systems also reduce wild fish supplies through habitat modification, wild seedstock collection and other ecological impacts. On balance, global aquaculture production still adds to world fish supplies; however, if the growing aquaculture industry is to sustain its contribution to world fish supplies, it must reduce wild fish inputs in feed and adopt more ecologically sound management practices. 相似文献
520.
A triclosan-resistant bacterial enzyme 总被引:22,自引:0,他引:22