全文获取类型
收费全文 | 2860篇 |
免费 | 161篇 |
国内免费 | 155篇 |
专业分类
3176篇 |
出版年
2024年 | 6篇 |
2023年 | 39篇 |
2022年 | 50篇 |
2021年 | 56篇 |
2020年 | 80篇 |
2019年 | 103篇 |
2018年 | 103篇 |
2017年 | 61篇 |
2016年 | 63篇 |
2015年 | 80篇 |
2014年 | 120篇 |
2013年 | 200篇 |
2012年 | 72篇 |
2011年 | 114篇 |
2010年 | 71篇 |
2009年 | 90篇 |
2008年 | 112篇 |
2007年 | 125篇 |
2006年 | 140篇 |
2005年 | 122篇 |
2004年 | 117篇 |
2003年 | 87篇 |
2002年 | 105篇 |
2001年 | 80篇 |
2000年 | 82篇 |
1999年 | 72篇 |
1998年 | 67篇 |
1997年 | 67篇 |
1996年 | 57篇 |
1995年 | 46篇 |
1994年 | 33篇 |
1993年 | 56篇 |
1992年 | 58篇 |
1991年 | 49篇 |
1990年 | 51篇 |
1989年 | 45篇 |
1988年 | 45篇 |
1987年 | 38篇 |
1986年 | 35篇 |
1985年 | 34篇 |
1984年 | 22篇 |
1983年 | 23篇 |
1982年 | 31篇 |
1981年 | 19篇 |
1980年 | 21篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
排序方式: 共有3176条查询结果,搜索用时 0 毫秒
71.
Shiran Barber-Zucker Jenny Hall Afonso Froes Sofiya Kolusheva Fraser MacMillan Raz Zarivach 《The Journal of biological chemistry》2020,295(49):16614
Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM''s CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation. 相似文献
72.
Philip J. White Timothy S. George Peter J. Gregory A. Glyn Bengough Paul D. Hallett Blair M. McKenzie 《Annals of botany》2013,112(2):207-222
Background
Plants form the base of the terrestrial food chain and provide medicines, fuel, fibre and industrial materials to humans. Vascular land plants rely on their roots to acquire the water and mineral elements necessary for their survival in nature or their yield and nutritional quality in agriculture. Major biogeochemical fluxes of all elements occur through plant roots, and the roots of agricultural crops have a significant role to play in soil sustainability, carbon sequestration, reducing emissions of greenhouse gasses, and in preventing the eutrophication of water bodies associated with the application of mineral fertilizers.Scope
This article provides the context for a Special Issue of Annals of Botany on ‘Matching Roots to Their Environment’. It first examines how land plants and their roots evolved, describes how the ecology of roots and their rhizospheres contributes to the acquisition of soil resources, and discusses the influence of plant roots on biogeochemical cycles. It then describes the role of roots in overcoming the constraints to crop production imposed by hostile or infertile soils, illustrates root phenotypes that improve the acquisition of mineral elements and water, and discusses high-throughput methods to screen for these traits in the laboratory, glasshouse and field. Finally, it considers whether knowledge of adaptations improving the acquisition of resources in natural environments can be used to develop root systems for sustainable agriculture in the future. 相似文献73.
Ta-Hsien Lin Horng-Dar Lin Jeng-Ling Yang Vladimir R. Kaberdin Sue Lin-Chao Tai-huang Huang 《Journal of biomolecular structure & dynamics》2013,31(4):677-685
Abstract We have synthesized two RNA fragments: a 42-mer corresponding to the full loop I sequence of the loop I region of ColE1 antisense RNA (RNA I), plus three additional Gs at the 5′-end, and a 31-mer which has 11 5′-end nucleotides (G(-2)-U9) deleted. The secondary structure of the 42-mer, deduced from one- and two-dimensional NMR spectra, consists of a stem of 11 base-pairs which contains a U-U base-pair and a bulged C base, a 7 nucleotide loop, and a single-stranded 5′ end of 12 nucleotides. The UV-melting study of the 42-mer further revealed a multi-step melting behavior with transition temperatures 32°C and 71°C clearly discernible. In conjunction with NMR melting study the major transition at 71°C is assigned to the overall melting of the stem region and the 32°C transition is assigned to the opening of the loop region. The deduced secondary structure agrees with that proposed for the intact RNA I and provides structural bases for understanding the specificity of RNase E. 相似文献
74.
Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 h following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP)/(ATP + ADP + AMP)] when compared to controls. However, after 4 h of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. 相似文献
75.
Robert L. Nakamura 《Molecular membrane biology》2013,30(5-7):293-308
Kat1 is a highly selective inward-rectifying K+ channel that opens for extended periods under conditions of extreme hyperpolarization. Over 200 point mutants in the pore region of the Kat1 K+ channel were generated and examined in the yeast Saccharomyces cerevisiae and Xenopus oocytes to assess the effect of the mutations on ion selectivity. Substitutions at the tyrosine of the signature sequence G-Y-G resulted in the most significant alterations in ion selectivity, consistent with its role in the selectivity filter. However, greater than 80% of the mutations throughout the greater pore region also conferred a defect in selectivity demonstrating that the entire pore of Kat1 contributes to the ion selectivity of this channel. Surprisingly, we identified a novel class of mutant channel that conferred enhanced selectivity of K+ over Na+. Mutants of this class frequently displayed sensitivity to the competing ion Cs+. This finding has led us to speculate that the Kat1 channel pore has evolved to balance not only K+/Na+ selectivity, but selectivity over Cs+, and possibly a wide spectrum of potential competing ions. 相似文献
76.
《Molecular membrane biology》2013,30(1-2):43-60
Based on published evidence that cation transport in mitochondria is not significantly dependent on a membrane potential, it is suggested that the process of mitochondrial cation transport may be nonelectrogenic. These experiments focused on the possibility that K+ flux into rat liver mitochondria may be directly coupled, via an energy-linked carrier mechanism, to OH? influx or H+ efflux. The dependence of the unidirectional K+ influx on the external K+ concentration indicates involvement of a saturable mechanism. Increasing the external pH from 7.0 to 8.0 increases the apparent Vmax of the K+ influx without significantly altering the apparent Km for K+. The pH dependence is greater in the presence of N-ethyl maleimide, a known inhibitor of the mitochondrial Pi/OH? exchange mechanism. N-Ethyl maleimide decreases the apparent Vmax at pH 7.0 and increases it at pH 8.0. Evidence indicates that both N-ethyl maleimide and a high external Pi concentration may stimulate the K+ influx at alkaline external pH (8.0) by preventing net exchanges between endogenous Pi and external OH?. An apparent first-order dependence of the K+ influx on the external OH? concentration is observed in the presence of N-ethyl maleimide. These results are consistent with a possible role of external OH? as a cosubstrate of the K+ transport mechanism. 相似文献
77.
《Journal of Physiology》2013,107(6):471-482
Executive function is a product of the coordinated operation of multiple neural systems and an essential prerequisite for a variety of cognitive functions. The prefrontal cortex is known to be a key structure for the performance of executive functions. To accomplish the coordinated operations of multiple neural systems, the prefrontal cortex must monitor the activities in other cortical and subcortical structures and control and supervise their operations by sending command signals, which is called top-down signaling. Although neurophysiological and neuroimaging studies have provided evidence that the prefrontal cortex sends top-down signals to the posterior cortices to control information processing, the neural correlate of these top-down signals is not yet known. Through use of the paired association task, it has been demonstrated that top-down signals are used to retrieve specific information stored in long-term memory. Therefore, we used a paired association task to examine the neural correlates of top-down signals in the prefrontal cortex. The preliminary results indicate that 32% of visual neurons exhibit pair-selectivity, which is similar to the characteristics of pair-coding activities in temporal neurons. The latency of visual responses in prefrontal neurons was longer than bottom-up signals but faster than top-down signals in inferior temporal neurons. These results suggest that pair-selective visual responses may be top-down signals that the prefrontal cortex provides to the temporal cortex, although further studies are needed to elucidate the neural correlates of top-down signals and their characteristics to understand the neural mechanism of executive control by the prefrontal cortex. 相似文献
78.
79.
Traditionally the hERG1 potassium channel has been known to have a fundamental role in membrane excitability of several mammalian cells including cardiac myocytes. hERG1 has recently been found to be expressed in non-excitable cancer cells of different histogenesis, but the role of this channel in cancer biology is unknown. Results form recent studies on the effect hERG1 inhibition in some breast cancer cells are controversial as it can lead to apoptosis or protect against cell death. Nevertheless, these data suggest that the hERG1 channel could have an important role in cancer biology. Here we report the effects of hyperstimulation of hERG1 channel in human mammary gland adenocarcinoma-derived cells. Application of the hERG1 activator, the diphenylurea derivative NS1643, inhibits cell proliferation irreversibly. This event is accompanied by a preferential arrest of the cell cycle in G0/G1 phase without the occurrence of apoptotic events. Consequently, cells responded to NS1643 by developing a senescence-like phenotype associated with increased protein levels of the tumor suppressors p21 and p16INK4a and by a positive β-galactosidase assay. These data suggest that prolonged stimulation of the hERG1 potassium channel may activate a senescence program and offers a compelling opportunity to develop a potential antiproliferative cancer therapy. 相似文献
80.
León D. Islas 《Channels (Austin, Tex.)》2016,10(3):202-213
Voltage-gated potassium channels or Kv's are membrane proteins with fundamental physiological roles. They are composed of 2 main functional protein domains, the pore domain, which regulates ion permeation, and the voltage-sensing domain, which is in charge of sensing voltage and undergoing a conformational change that is later transduced into pore opening. The voltage-sensing domain or VSD is a highly conserved structural motif found in all voltage-gated ion channels and can also exist as an independent feature, giving rise to voltage sensitive enzymes and also sustaining proton fluxes in proton-permeable channels. In spite of the structural conservation of VSDs in potassium channels, there are several differences in the details of VSD function found across variants of Kvs. These differences are mainly reflected in variations in the electrostatic energy needed to open different potassium channels. In turn, the differences in detailed VSD functioning among voltage-gated potassium channels might have physiological consequences that have not been explored and which might reflect evolutionary adaptations to the different roles played by Kv channels in cell physiology. 相似文献