全文获取类型
收费全文 | 1379篇 |
免费 | 121篇 |
国内免费 | 81篇 |
出版年
2024年 | 6篇 |
2023年 | 39篇 |
2022年 | 55篇 |
2021年 | 55篇 |
2020年 | 45篇 |
2019年 | 89篇 |
2018年 | 73篇 |
2017年 | 49篇 |
2016年 | 57篇 |
2015年 | 48篇 |
2014年 | 70篇 |
2013年 | 126篇 |
2012年 | 57篇 |
2011年 | 72篇 |
2010年 | 49篇 |
2009年 | 56篇 |
2008年 | 79篇 |
2007年 | 72篇 |
2006年 | 85篇 |
2005年 | 49篇 |
2004年 | 48篇 |
2003年 | 35篇 |
2002年 | 22篇 |
2001年 | 24篇 |
2000年 | 17篇 |
1999年 | 18篇 |
1998年 | 13篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 22篇 |
1994年 | 11篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1973年 | 4篇 |
排序方式: 共有1581条查询结果,搜索用时 31 毫秒
1.
Linda Partridge 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1537):147-154
Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development. 相似文献
2.
M.A. Mena M.J. Casarejos J.A. Rodríguez-Navarro I. Rodal J.G. de Yebenes 《FEBS letters》2009,583(1):168-174
Parkin mutations produce Parkinson’s disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H2O2 toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO).NP7, 5-10 μM, prevented the H2O2 induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H2O2 induced drop-out of dopamine neurons. Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H2O2. NP7 may be a promising neuroprotector against oxidative stress in PD. 相似文献
3.
皮肤作为人体最大器官覆盖于全身,能阻挡有害物质的侵入,保护人体内环境稳态,参与人体代谢过程。皮肤损伤、炎症和纤维化等,都会导致皮肤屏障功能的减退,影响正常的生命活动。溶血磷脂酸(lysophosphatidic acid,LPA)是十分活跃的磷脂信号分子,参与多种生理和病理生理过程。LPA是维持体内平衡所必需的生物活性脂质介质,在皮肤中通过不同的信号通路发挥多功能磷脂信使作用。本文综述了皮肤中溶血磷脂酸受体(lysophosphatidic acid receptor,LPA1-6)及其细胞信号通路的作用及机制,综述了LPA在皮肤创面愈合、皮肤瘢痕、皮肤黑色素瘤、硬皮病、皮肤瘙痒、过敏性皮炎、皮肤屏障、皮肤疼痛,皮肤毛发生长中的作用及分子机制,有助于了解LPA在皮肤中的生理和病理生理作用。深入研究LPA的作用机制将有助于挖掘其在皮肤治疗中的作用,开发以LPA为靶点的药物。 相似文献
4.
This scanning-electron microscopic study demonstrates the convergent evolution of the mouthparts of various herbivorous stream animals (insects from different orders, an isopod, snails, fish, and a tadpole) feeding on epilithic algal pastures. This food source is rich but is often difficult to harvest. Nevertheless, a large number of species can live on it because they have evolved highly specialized mouthparts. There are four functional problems that an algae grazer has to solve: the algae must be removed from the stone, they have to be collected and crushed, and a current shield is needed to prevent the water flow sweeping away the food. Among the 30 algae grazers examined in this study, a limited number of morphological solutions have been found for each of these adaptational problems. There are multiple evolutionary pathways for mouthpart adaptation and even closely related species have often evolved different types of tools for the same function. This refects the existence of a certain amount of evolutionary scope. Such freedom of evolution is present, however, only at the beginning of the adaptiogenesis of an algae grazer. Once one of the evolutionary pathways is taken, further improvement of the mouthparts is possible only by the refinement of the ‘chosen’ type of tools. The consequence of this is that a large number of astonishing convergences have occurred in algae grazers that have independently trodden the same evolutionary pathway. 相似文献
5.
Are the carbon costs of seed production related to the quantitative and qualitative performance? An appraisal for legumes and other crops 总被引:1,自引:0,他引:1
In the past great efforts have been made to gain a thorough understanding of the processes involved in carbon fixation but the fate of the acquired carbon has been somewhat neglected, although this aspect is crucial for improving yield performance without diminishing the quality of the harvested organs. To contribute to the crucial debate on that topic the aim of the present study was to propose some unbiased components concerning in particular grain legumes: ‘Is there any antagonism between high yield and increased nutritional quality, with a focus on protein content?’ An original approach has been used to study the impact of the modification of seed composition on the crop production, which combines theoretical calculations of energetic cost and field yield data. When applied to a wide range of species with varying seed composition, a plurispecific negative relationship between the theoretical carbon costs of seed production and the observed yields was demonstrated. The high-throughput of genetic markers could result in large-scale screening of seed quality parameters and such studies, while evaluating the impact of seed composition on crop yield, could also be used to provide data to forecast the economic impact of a new line with an original composition compared with its economically enhanced value. 相似文献
6.
Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat 总被引:19,自引:0,他引:19
Summary The lumen of the small intestine in anesthetized rats was recirculated with 50 ml perfusion fluid containing normal salts, 25mm glucose and low concentrations of hydrophilic solutes ranging in size from creatinine (mol wt 113) to Inulin (mol wt 5500). Ferrocyanide, a nontoxic, quadrupally charged anion was not absorbed; it could therefore be used as an osmotically active solute with reflection coefficient of 1.0 to adjust rates of fluid absorption,J
v
, and to measure the coefficient of osmotic flow,L
p
. The clearances from the perfusion fluid of all other test solutes were approximately proportional toJ
v
. FromL
p
and rates of clearances as a function ofJ
v
and molecular size we estimate (a) the fraction of fluid absorption which passes paracellularly (approx. 50%), (b) coefficients of solvent drag of various solutes within intercellular junctions, (c) the equivalent pore radius of intercellular junctions (50 Å) and their cross sectional area per unit path length (4.3 cm per cm length of intestine). Glucose absorption also varied as a function ofJ
v
. From this relationship and the clearances of inert markers we calculate the rate of active transport of glucose, the amount of glucose carried paracellularly by solvent drag or back-diffusion at any givenJ
v
and luminal glucose concentration and the concentration of glucose in the absorbate. The results indicate that solvent drag through paracellular channels is the principal route for intestinal transport of glucose or amino acids at physiological rates of fluid absorption and concentration. In the absence of luminal glucose the rate of fluid absorption and the clearances of all inert hydrophilic solutes were greatly reduced. It is proposed that Na-coupled transport of organic solutes from lumen to intercellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag. Further evidence for regulation of channel width is provided in accompanying papers on changes in electrical impedance and ultrastructure of junctions during Na-coupled solute transport. 相似文献
7.
A. K. Vidybida 《European biophysics journal : EBJ》1989,16(6):357-361
A theoretical model is proposed to describe the influence of a periodic electric field (PEF) upon a biopolymer. The biopolymer is treated as a classical mechanical system consisting of subsystems (molecular groups) which interact with each other through potential forces. The PEF is treated as a periodic driving force applied to a molecular group. The energy dissipation is considered using the model of fluid (viscous) friction. Arguments for the non-linear character of the friction-velocity dependence caused by the non-Newtonian rheology of a viscous medium are formulated.A forced molecular-group motion is investigated for the situation of a small driving-force period, with oscillations overdamped and a driving force consisting of more than one harmonic. As a result, it is established that the motion always gets to a terminal stage when only a small-scale vibration about some point, X
*, takes place. The terminal motion is preceded by a transient characterized by the presence of a directional velocity component and so by a drift along a potential profile. the drift goes on until a barrier is met which has a sufficiently large steepness (the barrier height is not important). As a result, the point X
* may happen to be remote from the conformation potential local minimum (conformational state). The physical reasons for the drift are described.If we consider the small-scale vibration about X
* in the framework of the hierarchy of scales for intramolecular mobility, it can be regarded as an equilibrium mobility, whereas the drift can be regarded as a functionally important motion, and X
* as a new conformational state which is realizable only in the presence of the PEF. It may be concluded, as the result of a consistent treatment and neglecting the small-scale vibration, that the conformational potential is modified by adding a linear term (in the one-dimensional case). In this connection, the set of conformational states can both deform (deviation of the positions of minima and their relative depth) and rearrange qualitatively (some minima can vanish and/or new minima can appear). In particular, the transition from one conformation to another one may happen due to rearrangement. 相似文献
8.
Michael R. Blatt 《Planta》1988,174(2):187-200
Fusicoccin (FC) is commonly thought to promote electrogenic H+ extrusion through its action on the H+-ATPase of the plant plasma membrane. Nonetheless, essential support from rigorous electrophysiological analysis has remained largely absent. The present investigation surveys the effects of FC on the charge transport properties at the membrane of a higher-plant cell — stomatal guard cells of Vicia faba L. — for which the electrical geometry is defined, and from which the voltage-dependent kinetic characteristic for the pump has been identified. Current-voltage (I-V) relations of the guard cells were determined before and during treatments with FC, and during brief exposures to NaCN plus salicylhydroxamic acid. Responses of the pump and of the ensemble of secondary transport processes were identified in the whole-membrane conductance-voltage relations and in the difference-current-voltage (dI-V) characteristic for the pump. In 0.1 mM K+, exposure to 10 M FC shifted guard-cell potentials negative by 29–61 mV. Current-and conductance-voltage profiles indicated limited changes in the pump I-V characteristic, an observation which was confirmed through explicit kinetic analysis of pump dI-V relations. However, the voltage response was accompanied by a 1.5-to 2.6-fold fall in membrane conductance. These results challenge conventional views of fusicoccin action by ascribing the electrical responses to reduced current passage through secondary transport pathways as well as to enhanced electrogenic ion pumping.Abbreviations and symbols Hepes
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- SHAM
salicylhydroxamic acid
- FC
fusicoccin
-
V
m
free-running membrane potential
-
G
m
membrane slope conductance at V
m
- (d)I-V
(difference) current-voltage (relation)
-
G-V
slope conductance-voltage (relation) 相似文献
9.
Microbial growth on carbon monoxide 总被引:14,自引:0,他引:14
The utilization of carbon monoxide as energy and/or carbon source by different physiological groups of bacteria is described and compared. Utilitarian CO oxidation which is coupled to the generation of energy for growth is achieved by aerobic and anaerobic eu- and archaebacteria. They belong to the physiological groups of aerobic carboxidotrophic, facultatively anaerobic phototrophic, and anaerobic acetogenic, methanogenic or sulfate-reducing bacteria. The key enzyme in CO oxidation is CO dehydrogenase which is a molybdo iron-sulfur flavoprotein in aerobic CO-oxidizing bacteria and a nickel-containing iron-sulfur protein in anaerobic ones. In carboxidotrophic and phototrophic bacteria, the CO-born CO2 is fixed by ribulose bisphosphate carboxylase in the reductive pentose phosphate cycle. In acetogenic, methanogenic, and probably in sulfate-reducing bacteria, CODH/acetyl-CoA synthase directly incorporates CO into acetyl-CoA.In plasmid-harbouring carboxidotrophic bacteria, CO dehydrogenase as well as enzymes involved in CO2 fixation or hydrogen utilization are plasmid-encoded. Structural genes encoding CO dehydrogenase were cloned from carboxidotrophic, acetogenic and methanogenic bacteria. Although they are clustered in each case, they are genetically distinct.Soil is a most important biological sink for CO in nature. While the physiological microbial groups capable of CO oxidation are well known, the type and nature of the microorganisms actually representing this sink are still enigmatic. We also tried to summarize the little information available on the nutritional and physicochemical requirements determining the sink strength. Because CO is highly toxic to respiring organisms even in low concentrations, the function of microbial activities in the global CO cycle is critical. 相似文献
10.
The accumulation of transported materials in cut axons is demonstrated by the light and electron microscopic immunocytochemical localization of substance P and enkephalin in the caudal medulla and cervical spinal cord of adult rat. Two days following unilateral knife-cuts in the caudal medulla or spinal (C2-C3) levels, substance P and enkephalin-like immunoreactivity (SPLI and ELI) are detected in lesioned axons located rostral and caudal to the transection. Rostrally, SPLI and ELI are detected in the lateral reticular region and ventrolateral fasciculus corresponding to the location of previously identified bulbospinal pathways. Caudally, previously unidentified, propriospinal pathways showing SPLI are detected in the dorsal columns and in the dorsolateral fasciculus. In contrast, ELI is found caudal to the transection only in the reticular region of the medulla. For both peptides, immunoreactivity is present throughout axons containing numerous large, dense core, and small clear vesicles. These results support the concept of both particulate and soluble modes of transport for substance P and enkephalin within axons of the central nervous system. 相似文献