全文获取类型
收费全文 | 5904篇 |
免费 | 500篇 |
国内免费 | 933篇 |
出版年
2024年 | 8篇 |
2023年 | 89篇 |
2022年 | 119篇 |
2021年 | 160篇 |
2020年 | 196篇 |
2019年 | 244篇 |
2018年 | 232篇 |
2017年 | 204篇 |
2016年 | 193篇 |
2015年 | 197篇 |
2014年 | 302篇 |
2013年 | 388篇 |
2012年 | 268篇 |
2011年 | 346篇 |
2010年 | 224篇 |
2009年 | 322篇 |
2008年 | 310篇 |
2007年 | 370篇 |
2006年 | 320篇 |
2005年 | 305篇 |
2004年 | 214篇 |
2003年 | 216篇 |
2002年 | 197篇 |
2001年 | 148篇 |
2000年 | 141篇 |
1999年 | 161篇 |
1998年 | 112篇 |
1997年 | 129篇 |
1996年 | 110篇 |
1995年 | 89篇 |
1994年 | 83篇 |
1993年 | 94篇 |
1992年 | 88篇 |
1991年 | 58篇 |
1990年 | 79篇 |
1989年 | 68篇 |
1988年 | 53篇 |
1987年 | 48篇 |
1986年 | 48篇 |
1985年 | 55篇 |
1984年 | 67篇 |
1983年 | 42篇 |
1982年 | 64篇 |
1981年 | 43篇 |
1980年 | 39篇 |
1979年 | 29篇 |
1978年 | 13篇 |
1977年 | 18篇 |
1975年 | 8篇 |
1973年 | 8篇 |
排序方式: 共有7337条查询结果,搜索用时 328 毫秒
951.
952.
Protection from Cell Death by mcl-1 Is Mediated by Membrane Hyperpolarization Induced By K+ Channel Activation 总被引:3,自引:0,他引:3
Mcl-1, a member of the Bcl-2 family, has been identified as an inhibitor of apoptosis induced by anticancer agents and radiation in myeloblastic leukemia
cells. The molecular mechanism underlying this phenomenon, however, is not yet understood. In the present study, we report
that hyperpolarization of the membrane potential is required for prevention of mcl-1 mediated cell death in murine myeloblastic FDC-P1 cells. In cells transfected with mcl-1, the membrane potential, measured by the whole-cell patch clamp, was hyperpolarized more than −30 mV compared with control
cells. The membrane potential was repolarized by increased extracellular K+ concentration (56 mV per 10-fold change in K+ concentration). Using the cell-attached patch-clamp technique, K+ channel activity was 1.7 times higher in mcl-1 transfected cells (NP
o
= 22.7 ± 3.3%) than control cells (NP
o
= 13.2 ± 1.9%). Viabilities of control and mcl-1 transfected cells after treatment with the cytotoxin etoposide (20 μg/ml), were 37.9 ± 3.9% and 78.2 ± 2.0%, respectively.
Suppression of K+ channel activity by 4-aminopyridine (4-AP) before etoposide treatment significantly reduced the viability of mcl-1 transfected cells to 49.0 ± 4.6%. These results indicate that as part of the prevention of cell death, mcl-1 causes a hyperpolarization of membrane potential through activation of K+ channel activity.
Received: 30 March 1999/Revised: 20 July 1999 相似文献
953.
Yuri V. Kim David L. Conover W. Gregory Lotz Stephen F. Cleary 《Bioelectromagnetics》1998,19(6):366-376
The mechanism of biological effects of extremely-low-frequency electric and magnetic fields may involve induced changes of Ca2+ transport through plasma membrane ion channels. In this study we investigated the effects of externally applied, low-intensity 60 Hz electric (E) fields (0.5 V/m, current density 0.8 A/m2+) on the agonist-induced Ca2+ fluxes of HL-60 leukemia cells. The suspensions of HL-60 cells received E-field or sham exposure for 60 min and were simultaneously stimulated either by 1 μM ATP or by 100 μM histamine or were not stimulated at all. After E-field or sham exposure, the responses of the intracellular calcium levels of the cells to different concentrations of ATP (0.2–100 μM) were assessed. Compared with control cells, exposure of ATP-activated cells to an E-field resulted in a 20–30% decrease in the magnitude of [Ca2+]i elevation induced by a low concentration of ATP (<1 μM). In contrast, exposure of histamine-activated HL-60 cells resulted in a 20–40% increase of ATP-induced elevation of [Ca2+]i. E-field exposure had no effect on non-activated cells. Kinetic analysis of concentration-response plots also showed that compared with control cells, exposure to the E-field resulted in increases of the Michaelis constant, Km, value in ATP-treated cells and of the maximal [Ca2+]i peak rise in histamine-treated HL-60 cells. The observed effects were reversible, indicating the absence of permanent structural damages induced by acute 60 min exposure to electric fields. These results demonstrate that low-intensity electric fields can alter calcium distribution in cells, most probably due to the effect on receptor-operated Ca2+ and/or ion channels. Bioelectromagnetics 19:366–376, 1998. © 1998 Wiley-Liss, Inc. 相似文献
954.
Eric Le Cam Dominique Coulaud Etienne Delain Patrice Petitjean Bernard P. Roques Dominique Grard Elena Stoylova Constance Vuilleumier Stoyl P. Stoylov Yves Mly 《Biopolymers》1998,45(3):217-229
NCp7, the nucleocapsid protein of the human immunodeficiency virus type 1, induces an ordered aggregation of RNAs, a mechanism that is thought to be involved in the NCp7-induced promotion of nucleic acid annealing. To further investigate this aggregation, the morphology and the properties of the NCp7-induced aggregates of the model RNA homoribopolymer, polyA, were investigated by electron microscopy in various conditions. In almost all the tested conditions, the aggregates were spherical and consisted of a central dense core surrounded by a less dense halo made of NCp7-covered polyA molecules. The formation of these aggregates with a narrow distribution of sizes constitutes a distinctive feature of NCp7 over other single-stranded nucleic acid binding proteins. In most conditions, at the shortest times that can be reached experimentally, all the polyA molecules were already incorporated in small aggregates, suggesting that the nucleation step and the first aggregation events took place rapidly. The aggregates then orderly grew with time by fusion of the smaller aggregates to give larger ones. The aggregate halo was important in the fusion process by initiating the bridging between the colliding aggregates. In the presence of an excess of protein, the aggregates grew rapidly but were loosely packed and dissociated easily, suggesting adverse protein-protein interactions in the aggregates obtained in these conditions. In the presence of an excess of nucleotides, the presence of both amorphous nonspherical and slowly growing spherical aggregates suggested some changes in the mechanism of aggregate growth due to an incomplete covering of polyA molecules by NCp7. Finally, we showed that in the absence of added salt, the aggregate fusions were unfavored but not the initial events giving the first aggregates, the reverse being true in the presence of high salt concentrations (≥300 mM). © 1998 John Wiley & Sons, Inc. Biopoly 45: 217–229, 1998 相似文献
955.
Morgan Stefansson 《Biopolymers》1999,49(6):515-524
During capillary electrophoresis of negatively charged polysaccharides in polymer solutions as sieving media, concentration fluctuations develop due to electrohydrodynamic instabilities caused by polarization of the polyelectrolytic chains. This leads to deviations from electroneutrality far beyond the Debye layer and segregation of the initially homogeneous sample solution into aggregated sample‐rich domains as verified by epifluorescence videomicroscopy imaging. As a result, anomalous and irregular peak profiles are obtained impeding the characterization of such complex sample mixtures. This effect appears at an electric field strength threshold value that depends on the molecular weight of the solute polymer molecules, pH, type and concentration of the polymer solution sieving media, and buffering conditions. The magnitude increases with increasing field strength and amount of sample injected. The aggregation onset, as evaluated by the value of the threshold potential, is affected by the charge density of the sample polymer molecules and Debye screening effects and investigated through variation of pH and ionic strength, respectively. Exchange of a simple base buffer component for small and multiply charged organic bases markedly increases the electric field strength necessary to trigger the electrohydrodynamic instabilities. Ultimately, the threshold value could be increased more than seven times by addition of an oppositely charged aminodextran polymer, thereby decreasing the analysis time. © 1999 John Wiley & Sons, Inc. Biopoly 49: 515–524, 1999 相似文献
956.
高氧对果蔬采后生理影响研究进展 总被引:4,自引:0,他引:4
高氧(21%-100%O2)贮藏是近几年发展起来的果蔬采后处理技术之一.概述了高氧对果蔬采后生理如呼吸作用、乙烯合成、组织褐变、活性氧代谢及抗氧化能力、风味等方面的影响,还介绍了高氧对病原微生物生长和采后果蔬腐烂控制的作用. 相似文献
957.
Hyun-seung Kim Jae Yup Jung KyungSu Kim Chihyun Hwang Jisang Yu Min-Sik Park Woosuk Cho 《Liver Transplantation》2024,14(14):2303965
Voids are widely disseminated in a powder when mixed, and hence the typical dry-electrode preparation method yields a sparse dry-electrode because the external pressure applied to the surface of the mixed powder is not evenly distributed. Consequently, particle cracking and void remnants appear in the electrode after calendaring. This study introduces a practically applicable bi-functionalized electrode additive to simultaneously reinforce the chemo-mechanical properties of millimeter-thick dry electrodes. The agyrodite Li6PS5Cl solid electrolyte and lithium difluorophosphate (LiPO2F2) additive have different sizes, as demonstrated by their densification from their elaborate bimodal structure, which is densely packed. Because the additive is filled into the interparticle voids in the electrode sheet during electrode fabrication, a decrease in electrode cracking after calendaring is possible because of the uniform distribution of external pressure. Hence, a thin, highly ionic/electronic-conductive electrode can be constructed by the addition of LiPO2F2 additive. Furthermore, during the formation, the active material surface-contacted LiPO2F2 promptly produces a surface layer comprising LiF and LixPFy. Thus, the addition of LiPO2F2 further reduces the degradation of Li6PS5Cl solid electrolytes. As a result, the LiPO2F2 additive simultaneously improves the electrochemical and physicochemical properties of millimeter-thick dry-electrodes for high-energy all-solid-state battery systems. 相似文献
958.
Yanjie Cheng Ziwei Zheng Shuang Liu Junwei Xiang Chuanzhou Han Minghao Xia Guodong Zhang Jianhang Qi Yongming Ma Kai Chen Yiran Tao Xinhui Lu Anyi Mei Hongwei Han 《Liver Transplantation》2024,14(8):2303988
Popular solution-processed approaches for producing the active layer of perovskite solar cells (PSCs) generally have to make compromise between crystallinity and compactness by inducing a rapid crystallization process with explosive nucleation and limited growth via removing solvent quickly. Here, a practical growth-dominated in-plane directional crystallization technique (IPDC) with a deeply retarded crystallization process for the scalable preparation of PSCs are reported. During the low-temperature annealing, a tiny chamber with a small height is built atop the wet perovskite precursor film to restrain the vertical diffusion and removal of solvent vapor. The chamber eliminates the vertical solvent vapor gradient and induce a horizonal in-plane gradient of solvent vapor pressure (SVP) toward the preset exhaust port which allows the slow escape of solvent vapor to outer space. In this way, nucleation is induced preferentially near the port and the as-formed heterogeneous nuclei then grow continuously and directionally. With IPDC, sufficient filling of perovskite with high crystallinity and obvious growth orientation is realized in non-ordered mesoporous scaffolds. An encouraging power conversion efficiency of 19.35% and 16.53% is achieved respectively for the 0.1 and 52.3-cm2 printable mesoscopic hole-conductor-free PSCs with carbon electrodes. 相似文献
959.
水肥互作对滴灌玉米氮素吸收、水氮利用效率及产量的影响 总被引:1,自引:2,他引:1
优化水、氮供应是实现作物高产与水肥资源高效利用的有效途径.本文研究了田间试验条件下,水(4500、6750、9000 m3·hm-2)、氮(0、225、330、435、540 kg·hm-2)互作对高密度(≥105000 株·hm-2)滴灌玉米干物质积累、氮素吸收及产量的影响.结果表明: 玉米干物质积累与吸氮量均随灌溉和施氮水平的增加明显升高,当施氮量大于435 kg·hm-2和灌溉量大于9000 m3·hm-2时则呈减少趋势.完熟期玉米干物质积累对灌水的响应表现为W6750(36359 kg·hm-2)>W9000(35077 kg·hm-2)>W4500(33451 kg·hm-2),施氮对玉米吸氮量的变化表现为N435(459.9 kg·hm-2)>N540(458.1 kg·hm-2)>N330(416.3 kg·hm-2)>N225(351.3 kg·hm-2),N435比N330、N220分别升高9.1%、32.7%,N540比N435降低0.6%.在施氮量0~435 kg·hm-2范围内,玉米最大氮素吸收速率随施氮量增加而升高,在施氮量为435 kg·hm-2时达最大(6.57 kg·hm-2·d-1).灌水与施氮均可显著增加玉米产量、穗粒数和穗粒质量,二者有明显的正交互作用,且以氮为主效应.在施氮0~435 kg·hm-2范围内,氮肥利用率随施氮量的增加而升高,此后反而降低;灌溉水分生产率随施氮量升高而增加,随灌水量增加而明显下降,灌溉定额为4500~6750 m3·hm-2时,灌溉水分生产率可达2.57~3.80 kg·m-3.玉米最高产量18072 kg·hm-2的施氮量为567.0 kg·hm-2.最佳经济施氮量为427.9~467.7 kg N·hm-2时,玉米产量在17109~17138 kg·hm-2,氮素偏生产力和氮肥利用率分别达122 kg N·hm-2和45.0%.水氮一体化施肥可实现滴灌玉米高产协同水、氮利用效率的共同提高. 相似文献
960.
Xiang-Yu Qi Yang Cao Ya-Li Li Ming-Guang Mo Lu Zhou De-Yong Ye 《Bioorganic & medicinal chemistry letters》2017,27(15):3511-3515
Sphingomyelin synthase (SMS) is a key enzyme in sphingomyelin biosynthetic pathway, whose activity is highly related to the atherosclerosis progression. SMS2 could serve as a promising therapeutic target for atherosclerosis. Based on the structure of lead compound D2, a series of oxazolopyridine derivatives were designed, synthesized, and their inhibitory activities against purified SMS1 and SMS2 enzymes were evaluated respectively. The representative molecules QY4 and QY16 possess micromolar inhibitory activities against SMS2 and excellent isoform preferences over SMS1, qualified to be selected as potential molecules in further discovery of specific SMS2 inhibitors. 相似文献