全文获取类型
收费全文 | 353篇 |
免费 | 6篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
教育与普及 | 3篇 |
理论与方法论 | 3篇 |
现状及发展 | 58篇 |
研究方法 | 39篇 |
综合类 | 251篇 |
自然研究 | 4篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 2篇 |
2012年 | 20篇 |
2011年 | 41篇 |
2010年 | 13篇 |
2009年 | 1篇 |
2008年 | 13篇 |
2007年 | 22篇 |
2006年 | 21篇 |
2005年 | 17篇 |
2004年 | 10篇 |
2003年 | 22篇 |
2002年 | 58篇 |
2001年 | 41篇 |
2000年 | 7篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1993年 | 5篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1964年 | 4篇 |
1961年 | 2篇 |
排序方式: 共有360条查询结果,搜索用时 15 毫秒
171.
The Hill equation and the origin of quantitative pharmacology 总被引:1,自引:0,他引:1
Rudolf Gesztelyi Judit Zsuga Adam Kemeny-Beke Balazs Varga Bela Juhasz Arpad Tosaki 《Archive for History of Exact Sciences》2012,66(4):427-438
This review addresses the 100-year-old Hill equation (published in January 22, 1910), the first formula relating the result
of a reversible association (e.g., concentration of a complex, magnitude of an effect) to the variable concentration of one
of the associating substances (the other being present in a constant and relatively low concentration). In addition, the Hill
equation was the first (and is the simplest) quantitative receptor model in pharmacology. Although the Hill equation is an
empirical receptor model (its parameters have only physico-chemical meaning for a simple ligand binding reaction), it requires
only minor a priori knowledge about the mechanism of action for the investigated agonist to reliably fit concentration-response
curve data and to yield useful results (in contrast to most of the advanced receptor models). Thus, the Hill equation has
remained an important tool for physiological and pharmacological investigations including drug discovery, moreover it serves
as a theoretical basis for the development of new pharmacological models. 相似文献
172.
Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease 总被引:5,自引:0,他引:5
D B Calne J W Langston W R Martin A J Stoessl T J Ruth M J Adam B D Pate M Schulzer 《Nature》1985,317(6034):246-248
The dopa analogue 6-fluorodopa (6-FD) used with positron emission tomography (PET) allows in vivo visualization of dopamine and its metabolites in nigrostriatal nerve endings. We have now found abnormal 6-FD scans in four subjects exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). None had parkinsonism. The results suggest subclinical damage to the nigrostriatal pathway. This is the first direct evidence that dopaminergic impairment can exist without clinical deficits. Here we discuss this finding in the context of the hypothesis that Parkinson's disease may stem from clinically silent damage to the substantia nigra, followed by slow attrition of neurones in this region because of its particular vulnerability to cell loss as a normal consequence of ageing. 相似文献
173.
Stefater JA Lewkowich I Rao S Mariggi G Carpenter AC Burr AR Fan J Ajima R Molkentin JD Williams BO Wills-Karp M Pollard JW Yamaguchi T Ferrara N Gerhardt H Lang RA 《Nature》2011,474(7352):511-515
Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching. 相似文献
174.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma 总被引:1,自引:0,他引:1
Varela I Tarpey P Raine K Huang D Ong CK Stephens P Davies H Jones D Lin ML Teague J Bignell G Butler A Cho J Dalgliesh GL Galappaththige D Greenman C Hardy C Jia M Latimer C Lau KW Marshall J McLaren S Menzies A Mudie L Stebbings L Largaespada DA Wessels LF Richard S Kahnoski RJ Anema J Tuveson DA Perez-Mancera PA Mustonen V Fischer A Adams DJ Rust A Chan-on W Subimerb C Dykema K Furge K Campbell PJ Teh BT Stratton MR Futreal PA 《Nature》2011,469(7331):539-542
175.
176.
Submillimetre galaxies reside in dark matter haloes with masses greater than 3 × 10(11) solar masses
Amblard A Cooray A Serra P Altieri B Arumugam V Aussel H Blain A Bock J Boselli A Buat V Castro-Rodríguez N Cava A Chanial P Chapin E Clements DL Conley A Conversi L Dowell CD Dwek E Eales S Elbaz D Farrah D Franceschini A Gear W Glenn J Griffin M Halpern M Hatziminaoglou E Ibar E Isaak K Ivison RJ Khostovan AA Lagache G Levenson L Lu N Madden S Maffei B Mainetti G Marchetti L Marsden G Mitchell-Wynne K Nguyen HT O'Halloran B Oliver SJ Omont A Page MJ Panuzzo P Papageorgiou A Pearson CP 《Nature》2011,470(7335):510-512
The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year. These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes. Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. A previous attempt at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model. Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500?μm. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M(min), such that log(10)[M(min)/M(⊙)] = 11.5(+0.7)(-0.2) at 350?μm, where M(⊙) is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe, and is lower than that predicted by semi-analytical models for galaxy formation. 相似文献
177.
178.
McDermott-Roe C Ye J Ahmed R Sun XM Serafín A Ware J Bottolo L Muckett P Cañas X Zhang J Rowe GC Buchan R Lu H Braithwaite A Mancini M Hauton D Martí R García-Arumí E Hubner N Jacob H Serikawa T Zidek V Papousek F Kolar F Cardona M Ruiz-Meana M García-Dorado D Comella JX Felkin LE Barton PJ Arany Z Pravenec M Petretto E Sanchis D Cook SA 《Nature》2011,478(7367):114-118
Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy. 相似文献
179.
Li W Bloom JS Podsiadlowski P Miller AA Cenko SB Jha SW Sullivan M Howell DA Nugent PE Butler NR Ofek EO Kasliwal MM Richards JW Stockton A Shih HY Bildsten L Shara MM Bibby J Filippenko AV Ganeshalingam M Silverman JM Kulkarni SR Law NM Poznanski D Quimby RM McCully C Patel B Maguire K Shen KJ 《Nature》2011,480(7377):348-350
Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system, but little is known of the precise nature of the companion star and the physical properties of the progenitor system. There are two classes of models: double-degenerate (involving two white dwarfs in a close binary system) and single-degenerate models. In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy. Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems, allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf. 相似文献
180.