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201.
Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts 总被引:1,自引:0,他引:1
Y Shiba S Fernandes WZ Zhu D Filice V Muskheli J Kim NJ Palpant J Gantz KW Moyes H Reinecke B Van Biber T Dardas JL Mignone A Izawa R Hanna M Viswanathan JD Gold MI Kotlikoff N Sarvazyan MW Kay CE Murry MA Laflamme 《Nature》2012,489(7415):322-325
Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair. 相似文献
202.
Two Earth-sized planets orbiting Kepler-20 总被引:1,自引:0,他引:1
Fressin F Torres G Rowe JF Charbonneau D Rogers LA Ballard S Batalha NM Borucki WJ Bryson ST Buchhave LA Ciardi DR Désert JM Dressing CD Fabrycky DC Ford EB Gautier TN Henze CE Holman MJ Howard A Howell SB Jenkins JM Koch DG Latham DW Lissauer JJ Marcy GW Quinn SN Ragozzine D Sasselov DD Seager S Barclay T Mullally F Seader SE Still M Twicken JD Thompson SE Uddin K 《Nature》2012,482(7384):195-198
Since the discovery of the first extrasolar giant planets around Sun-like stars, evolving observational capabilities have brought us closer to the detection of true Earth analogues. The size of an exoplanet can be determined when it periodically passes in front of (transits) its parent star, causing a decrease in starlight proportional to its radius. The smallest exoplanet hitherto discovered has a radius 1.42 times that of the Earth's radius (R(⊕)), and hence has 2.9 times its volume. Here we report the discovery of two planets, one Earth-sized (1.03R(⊕)) and the other smaller than the Earth (0.87R(⊕)), orbiting the star Kepler-20, which is already known to host three other, larger, transiting planets. The gravitational pull of the new planets on the parent star is too small to measure with current instrumentation. We apply a statistical method to show that the likelihood of the planetary interpretation of the transit signals is more than three orders of magnitude larger than that of the alternative hypothesis that the signals result from an eclipsing binary star. Theoretical considerations imply that these planets are rocky, with a composition of iron and silicate. The outer planet could have developed a thick water vapour atmosphere. 相似文献
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The determination of palaeo-elevation has emerged in the past 15 years as an important tool for constraining physical processes that govern the formation of mountain belts. Rowley and Currie report palaeo-elevations for the Lunpola basin within the Tibetan plateau and claim that these elevations are incompatible with 'mantle-thickening models' for mountain formation. We show here that their data do not support this conclusion and, indeed, are consistent with its opposite. The Tibetan plateau could have risen by a kilometre or more as its dense lower lithosphere sank into the underlying mantle. 相似文献
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The primate amygdala represents the positive and negative value of visual stimuli during learning 总被引:1,自引:0,他引:1
Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala. 相似文献
208.
Bild AH Yao G Chang JT Wang Q Potti A Chasse D Joshi MB Harpole D Lancaster JM Berchuck A Olson JA Marks JR Dressman HK West M Nevins JR 《Nature》2006,439(7074):353-357
The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer subtypes, recurrence of disease and response to specific therapies using DNA microarray-based gene expression signatures has been demonstrated in multiple studies. Various studies have also demonstrated the potential for using gene expression profiles for the analysis of oncogenic pathways. Here we show that gene expression signatures can be identified that reflect the activation status of several oncogenic pathways. When evaluated in several large collections of human cancers, these gene expression signatures identify patterns of pathway deregulation in tumours and clinically relevant associations with disease outcomes. Combining signature-based predictions across several pathways identifies coordinated patterns of pathway deregulation that distinguish between specific cancers and tumour subtypes. Clustering tumours based on pathway signatures further defines prognosis in respective patient subsets, demonstrating that patterns of oncogenic pathway deregulation underlie the development of the oncogenic phenotype and reflect the biology and outcome of specific cancers. Predictions of pathway deregulation in cancer cell lines are also shown to predict the sensitivity to therapeutic agents that target components of the pathway. Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics. 相似文献
209.
Résumé L'oxymétholone est un androgène synthétique qui stimule la régénération des tissus. Son action est plus efficace que celle du phényl-propionate-nandrolone, car elle produit le replacement des tissus dès les premiers stades de la régénération chez les mâles. De plus, elle a l'avantage de pouvoir être administrée oralement.
The authors wish to thank MissM. Tydd for technical assistance and Syntex Pharmaceuticals Limited for the supply of oxymetholone. 相似文献
The authors wish to thank MissM. Tydd for technical assistance and Syntex Pharmaceuticals Limited for the supply of oxymetholone. 相似文献
210.