全文获取类型
收费全文 | 6480篇 |
免费 | 65篇 |
国内免费 | 88篇 |
专业分类
系统科学 | 65篇 |
丛书文集 | 69篇 |
教育与普及 | 25篇 |
理论与方法论 | 15篇 |
现状及发展 | 2451篇 |
研究方法 | 303篇 |
综合类 | 3673篇 |
自然研究 | 32篇 |
出版年
2021年 | 48篇 |
2016年 | 47篇 |
2015年 | 66篇 |
2014年 | 75篇 |
2013年 | 128篇 |
2012年 | 189篇 |
2011年 | 209篇 |
2010年 | 108篇 |
2009年 | 92篇 |
2008年 | 171篇 |
2007年 | 206篇 |
2006年 | 160篇 |
2005年 | 133篇 |
2004年 | 152篇 |
2003年 | 118篇 |
2002年 | 128篇 |
2001年 | 220篇 |
2000年 | 186篇 |
1999年 | 142篇 |
1992年 | 119篇 |
1991年 | 76篇 |
1990年 | 89篇 |
1989年 | 74篇 |
1988年 | 75篇 |
1987年 | 86篇 |
1986年 | 59篇 |
1985年 | 103篇 |
1984年 | 94篇 |
1983年 | 81篇 |
1982年 | 63篇 |
1981年 | 58篇 |
1980年 | 74篇 |
1979年 | 188篇 |
1978年 | 147篇 |
1977年 | 124篇 |
1976年 | 116篇 |
1975年 | 126篇 |
1974年 | 162篇 |
1973年 | 134篇 |
1972年 | 139篇 |
1971年 | 176篇 |
1970年 | 212篇 |
1969年 | 160篇 |
1968年 | 172篇 |
1967年 | 141篇 |
1966年 | 148篇 |
1965年 | 113篇 |
1958年 | 68篇 |
1957年 | 47篇 |
1954年 | 47篇 |
排序方式: 共有6633条查询结果,搜索用时 546 毫秒
131.
关于Smarandache函数的一个猜想 总被引:3,自引:0,他引:3
乐茂华 《黑龙江大学自然科学学报》2007,24(5):687-688
对于正整数a,设S(a)是Smarandache函数。利用有关Goldbach猜想的结果证明了:对于任何正整数k,方程S(x1) S(x2) … S(xk)=S(x1 x2 … xk)都有无穷多组正整数解(x1,x2,…,xk). 相似文献
132.
目的观察金丝桃素对慢性病毒性心肌炎(VMC)小鼠心肌细胞凋亡及Fas/FasL蛋白表达的影响。方法Balb/C小鼠多次接种心肌柯萨奇段病毒复制慢性VMC模型,首次感染病毒45天后将存活小鼠分为模型组、金丝桃素组及氯沙坦组,同时设正常对照组.分别给予相应药物干预30天,采用原位末端标记法检测心肌细胞凋亡及免疫组化方法检测Fas/FasL蛋白表达。结果模型组心肌细胞凋亡率较正常组显著增加(P〈0.05),金丝桃素组和氯沙坦组凋亡率较模型组显著降低(P〈0.05)。模型组Fas/FasL蛋白表达较正常组显著增多(P〈0.01),金丝桃素组和氯沙坦组较模型组显著降低(P〈0.01)。结论金丝桃素保护心肌细胞与抑制VMC心肌细胞的凋亡.下调Fas/FasL蛋白表达有关。 相似文献
133.
I. Campia E. Gazzano G. Pescarmona D. Ghigo A. Bosia C. Riganti 《Cellular and molecular life sciences : CMLS》2009,66(9):1580-1594
Digoxin and ouabain are steroid drugs that inhibit the Na+/K+-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism
of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on
the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver
HepG2 cells, enhancing the activity and the expression of the
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect
was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost
in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol
for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver
cells.
Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009 相似文献
134.
V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
135.
In this article we consider the growing interest in recent years in the use of documentary strategies in the wold of contemporary art, film and performing arts and explore some of the central epistemological assumptions underpinning the persistent idea that the documentary should be equated with ‘non-fiction’. Following Stella Bruzzi we argue that if documentary theory maintains objectivity as the primary measure of value, it will inevitably and continuously arrive at the conclusion that the documentary genre is fundamentally flawed. Instead, we propose to move beyond the ‘realist epistemology’ of documentary theory and focus on the ‘documentary real’, i.e. the specific performativity of the reality constructed in and by the documentary genre. In the last paragraphs, we introduce the various articles that address the “documentary real” in this special issue. 相似文献
136.
Dmitri B. Papkovsky Ruslan I. Dmitriev 《Cellular and molecular life sciences : CMLS》2018,75(16):2963-2980
Molecular oxygen (O2) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O2 concentration, state of decreased O2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O2 gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given. 相似文献
137.
Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually,
more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains
several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological
conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has
been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on
certain snake venom components and their applications in health and disease.
Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006 相似文献
138.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
139.
Amundadottir LT Sulem P Gudmundsson J Helgason A Baker A Agnarsson BA Sigurdsson A Benediktsdottir KR Cazier JB Sainz J Jakobsdottir M Kostic J Magnusdottir DN Ghosh S Agnarsson K Birgisdottir B Le Roux L Olafsdottir A Blondal T Andresdottir M Gretarsdottir OS Bergthorsson JT Gudbjartsson D Gylfason A Thorleifsson G Manolescu A Kristjansson K Geirsson G Isaksson H Douglas J Johansson JE Bälter K Wiklund F Montie JE Yu X Suarez BK Ober C Cooney KA Gronberg H Catalona WJ Einarsson GV 《Nature genetics》2006,38(6):652-658
With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry. 相似文献
140.
Foser S Redwanz I Ebeling M Heizmann CW Certa U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2387-2396
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes. 相似文献