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61.
A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery 总被引:1,自引:0,他引:1
Keogh MC Kim JA Downey M Fillingham J Chowdhury D Harrison JC Onishi M Datta N Galicia S Emili A Lieberman J Shen X Buratowski S Haber JE Durocher D Greenblatt JF Krogan NJ 《Nature》2006,439(7075):497-501
One of the earliest marks of a double-strand break (DSB) in eukaryotes is serine phosphorylation of the histone variant H2AX at the carboxy-terminal SQE motif to create gammaH2AX-containing nucleosomes. Budding-yeast histone H2A is phosphorylated in a similar manner by the checkpoint kinases Tel1 and Mec1 (ref. 2; orthologous to mammalian ATM and ATR, respectively) over a 50-kilobase region surrounding the DSB. This modification is important for recruiting numerous DSB-recognition and repair factors to the break site, including DNA damage checkpoint proteins, chromatin remodellers and cohesins. Multiple mechanisms for eliminating gammaH2AX as DNA repair completes are possible, including removal by histone exchange followed potentially by degradation, or, alternatively, dephosphorylation. Here we describe a three-protein complex (HTP-C, for histone H2A phosphatase complex) containing the phosphatase Pph3 that regulates the phosphorylation status of gammaH2AX in vivo and efficiently dephosphorylates gammaH2AX in vitro. gammaH2AX is lost from chromatin surrounding a DSB independently of the HTP-C, indicating that the phosphatase targets gammaH2AX after its displacement from DNA. The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint. 相似文献
62.
化学发光自显影免疫印迹法(Western Blotting)检测绒山羊皮肤组织中催乳素受体蛋白 总被引:2,自引:0,他引:2
采集不同季节绒山羊皮肤组织样品,提取总蛋白,经聚丙烯酰胺凝胶电泳,将电泳结果转移到醋酸纤维薄膜,然后与催乳素抗体结合、辣根过氧化物酶标记二抗结合,后者作用于化学发光底物,暗室中置X-光胶片上自显影数分钟,经显影、定影,得到黑色曝光斑,根据胶片上曝光斑的位置确定出催乳素受体的分子量为87kD。根据不同时期样品黑斑的大小得出各时期催乳素受体表达量与绒毛生长趋势是一致的。 相似文献
63.
J. Jacob 《Cellular and molecular life sciences : CMLS》1947,3(6):241-243
Summary Rabbit muscular globulins soluble between the ionic strengths 0.15 and 0.35 are, in an almost native state, the and myosins ofDubuisson. The extractability of both, and, by salt solutions is greatly reduced when the rabbit muscle has been stimulated to exhaustion or poisoned with the sodium salt of monobromacetic acid till a state of rigor is obtained. This reduction however does not proceed in an absolutely similar way for and, indicating probable functional differences between these two myosins. The other soluble muscular proteins are practically not affected, as far as the method permits this to be assertained. 相似文献
64.
驾驶员个体差异是影响城市道路交通运营、效率及安全的一个重要因素之一。为了实现对驾驶员差异性的影响分析,采用驾驶模拟舱研究平台对驾驶员样本进行归类。研究分别选取了反映驾驶员特征的静态驾驶适性和动态驾驶适性两类,共计15个指标。采用因子分析的方法将相关指标归纳为驾驶员的5个类因子,并通过主成份分析的方法找出每类因子中的主导指标,并以此指标作为聚类分析的输入变量。结果表明聚类分析得到的三类驾驶员具有明显的各自特征。 相似文献
65.
由于风电、光电出力具有不确定性,因此会引起电网频率的较大波动,严重影响电能质量.为了保证含有新能源电力系统的稳定运行,特提出风光水储联合调度优化模型.首先,建立含新能源的电力系统优化调度数学模型,该模型追求系统机组耗量最小.在进行含新能源发电的电力系统优化调度中,可被用来调度的出力实际为满足负荷功率后,扣除新能源输出功率的那部分火电机组出力.算例结果表明,本文采取CVaR具有良好的性能;风电与光伏清洁能源机组并入系统中增加了日前调度的不确定性风险,但通过CVaR评估计算系统风险,采取有效的措施会使系统发电成本减少与碳排放量减少. 相似文献
66.
Gonzalez-Suarez E Jacob AP Jones J Miller R Roudier-Meyer MP Erwert R Pinkas J Branstetter D Dougall WC 《Nature》2010,468(7320):103-107
RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease. 相似文献
67.
68.
J. Jacob 《Cellular and molecular life sciences : CMLS》1946,2(3):110-111
Summary Saline extracts from rabbit's skeletal muscles obtained and dialyzed at the ionic strength 0.15 contain at least 11 electrophoretically distinct components. Five of these components (n, m, t, l, s) have properties which are comparable with some characteristics of the myogens ofWeber, another component (h) is probably myoalbumin. Muscular proteins which are more soluble at higher ionic strength are not homogenous: there must be not one but two or more electrophoretically different myosins. Much work is needed to establish accurate relations between electrophoretic and classical muscular proteins. 相似文献
69.
70.