全文获取类型
收费全文 | 707篇 |
免费 | 2篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 15篇 |
丛书文集 | 2篇 |
教育与普及 | 3篇 |
理论与方法论 | 13篇 |
现状及发展 | 86篇 |
研究方法 | 116篇 |
综合类 | 434篇 |
自然研究 | 49篇 |
出版年
2018年 | 5篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 19篇 |
2012年 | 66篇 |
2011年 | 106篇 |
2010年 | 14篇 |
2009年 | 8篇 |
2008年 | 49篇 |
2007年 | 53篇 |
2006年 | 49篇 |
2005年 | 52篇 |
2004年 | 46篇 |
2003年 | 39篇 |
2002年 | 56篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 5篇 |
1970年 | 5篇 |
1969年 | 2篇 |
1968年 | 7篇 |
1967年 | 7篇 |
1966年 | 5篇 |
1965年 | 7篇 |
排序方式: 共有718条查询结果,搜索用时 84 毫秒
1.
新的、高密度树木种植正在给林业生物技术带来迅速的变化。但是如果不能克服生态风险和经济障碍.这些新的方法或许永远也无法使用—— 相似文献
2.
k consisting of k clusters, with k > 2. Bottom-up agglomerative approaches are also commonly used to construct partitions,
and we discuss these in terms of worst-case performance for metric data sets. Our main contribution derives from a new restricted
partition formulation that requires each cluster to be an interval of a given ordering of the objects being clustered. Dynamic programming can optimally split such an ordering into a partition Pk for a large class of objectives that includes min-diameter. We explore a variety of ordering heuristics and show that our
algorithm, when combined with an appropriate ordering heuristic, outperforms traditional algorithms on both random and non-random
data sets. 相似文献
3.
4.
Zohra Dhouafli Karina Cuanalo-Contreras El Akrem Hayouni Charles E. Mays Claudio Soto Ines Moreno-Gonzalez 《Cellular and molecular life sciences : CMLS》2018,75(19):3521-3538
Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases. 相似文献
5.
Water capture by a desert beetle. 总被引:15,自引:0,他引:15
Some beetles in the Namib Desert collect drinking water from fog-laden wind on their backs. We show here that these large droplets form by virtue of the insect's bumpy surface, which consists of alternating hydrophobic, wax-coated and hydrophilic, non-waxy regions. The design of this fog-collecting structure can be reproduced cheaply on a commercial scale and may find application in water-trapping tent and building coverings, for example, or in water condensers and engines. 相似文献
6.
Milne JC Lambert PD Schenk S Carney DP Smith JJ Gagne DJ Jin L Boss O Perni RB Vu CB Bemis JE Xie R Disch JS Ng PY Nunes JJ Lynch AV Yang H Galonek H Israelian K Choy W Iffland A Lavu S Medvedik O Sinclair DA Olefsky JM Jirousek MR Elliott PJ Westphal CH 《Nature》2007,450(7170):712-716
Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes. 相似文献
7.
BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module 总被引:1,自引:0,他引:1
Park D Tosello-Trampont AC Elliott MR Lu M Haney LB Ma Z Klibanov AL Mandell JW Ravichandran KS 《Nature》2007,450(7168):430-434
Engulfment and subsequent degradation of apoptotic cells is an essential step that occurs throughout life in all multicellular organisms. ELMO/Dock180/Rac proteins are a conserved signalling module for promoting the internalization of apoptotic cell corpses; ELMO and Dock180 function together as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac, and thereby regulate the phagocyte actin cytoskeleton during engulfment. However, the receptor(s) upstream of the ELMO/Dock180/Rac module are still unknown. Here we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a receptor upstream of ELMO and as a receptor that can bind phosphatidylserine on apoptotic cells. BAI1 is a seven-transmembrane protein belonging to the adhesion-type G-protein-coupled receptor family, with an extended extracellular region and no known ligands. We show that BAI1 functions as an engulfment receptor in both the recognition and subsequent internalization of apoptotic cells. Through multiple lines of investigation, we identify phosphatidylserine, a key 'eat-me' signal exposed on apoptotic cells, as a ligand for BAI1. The thrombospondin type 1 repeats within the extracellular region of BAI1 mediate direct binding to phosphatidylserine. As with intracellular signalling, BAI1 forms a trimeric complex with ELMO and Dock180, and functional studies suggest that BAI1 cooperates with ELMO/Dock180/Rac to promote maximal engulfment of apoptotic cells. Last, decreased BAI1 expression or interference with BAI1 function inhibits the engulfment of apoptotic targets ex vivo and in vivo. Thus, BAI1 is a phosphatidylserine recognition receptor that can directly recruit a Rac-GEF complex to mediate the uptake of apoptotic cells. 相似文献
8.
9.
Mullighan CG Goorha S Radtke I Miller CB Coustan-Smith E Dalton JD Girtman K Mathew S Ma J Pounds SB Su X Pui CH Relling MV Evans WE Shurtleff SA Downing JR 《Nature》2007,446(7137):758-764
Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer. 相似文献
10.
Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases--pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators--caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues. 相似文献