全文获取类型
收费全文 | 38005篇 |
免费 | 116篇 |
国内免费 | 146篇 |
专业分类
系统科学 | 179篇 |
丛书文集 | 611篇 |
教育与普及 | 65篇 |
理论与方法论 | 154篇 |
现状及发展 | 16674篇 |
研究方法 | 1583篇 |
综合类 | 18306篇 |
自然研究 | 695篇 |
出版年
2013年 | 302篇 |
2012年 | 575篇 |
2011年 | 1248篇 |
2010年 | 246篇 |
2008年 | 682篇 |
2007年 | 769篇 |
2006年 | 733篇 |
2005年 | 781篇 |
2004年 | 837篇 |
2003年 | 672篇 |
2002年 | 702篇 |
2001年 | 1098篇 |
2000年 | 1034篇 |
1999年 | 747篇 |
1992年 | 697篇 |
1991年 | 507篇 |
1990年 | 566篇 |
1989年 | 555篇 |
1988年 | 537篇 |
1987年 | 542篇 |
1986年 | 586篇 |
1985年 | 764篇 |
1984年 | 549篇 |
1983年 | 444篇 |
1982年 | 418篇 |
1981年 | 420篇 |
1980年 | 492篇 |
1979年 | 1142篇 |
1978年 | 903篇 |
1977年 | 870篇 |
1976年 | 726篇 |
1975年 | 751篇 |
1974年 | 1054篇 |
1973年 | 920篇 |
1972年 | 988篇 |
1971年 | 1091篇 |
1970年 | 1474篇 |
1969年 | 1182篇 |
1968年 | 1089篇 |
1967年 | 1076篇 |
1966年 | 1007篇 |
1965年 | 732篇 |
1964年 | 249篇 |
1959年 | 405篇 |
1958年 | 762篇 |
1957年 | 510篇 |
1956年 | 430篇 |
1955年 | 369篇 |
1954年 | 456篇 |
1948年 | 301篇 |
排序方式: 共有10000条查询结果,搜索用时 9 毫秒
911.
Inositol 1,4,5-trisphosphate activates a channel from smooth muscle sarcoplasmic reticulum 总被引:35,自引:0,他引:35
Inositol 1,4,5-trisphosphate (InsP3) can initiate calcium release into the cytoplasm in a variety of cells. From experiments using permeabilized cells, membrane vesicles, and patch-clamp techniques, it has been suggested that InsP3 acts by directly opening calcium channels. Here, we show that InsP3 induced openings of channels in planar lipid bilayers into which vesicles made from aortic muscle sarcoplasmic reticulum (SR) were incorporated. Activation of channels by InsP3 was not observed when vesicles made from SR of cardiac or skeletal muscle were incorporated into planar lipid bilayers. The present study demonstrates for the first time unique properties of an InsP3-gated calcium channel in sarcoplasmic reticulum vesicles from vascular smooth muscle. This InsP3-activated channel from aortic SR differs strikingly from the calcium-gated calcium channel of striated muscle SR in single-channel conductance and pharmacology. 相似文献
912.
Multiple liquid crystal phases of DNA at high concentrations 总被引:3,自引:0,他引:3
DNA packaging in vivo is very tight, with volume concentrations approaching 70% w/v in sperm heads, virus capsids and bacterial nucleoids. The packaging mechanisms adopted may be related to the natural tendency of semi-rigid polymers to form liquid crystalline phases in concentrated solutions. We find that DNA forms at least three distinct liquid crystalline phases at concentrations comparable to those in vivo, with phase transitions occurring over relatively narrow ranges of DNA concentration. A weakly birefringent, dynamic, 'precholesteric' mesophase with microscopic textures intermediate between those of a nematic and a true cholesteric phase forms at the lowest concentrations required for phase separation. At slightly higher DNA concentrations, a second mesophase forms which is a strongly birefringent, well-ordered cholesteric phase with a concentration-dependent pitch varying from 2 to 10 micron. At the highest DNA concentrations, a phase forms which is two-dimensionally ordered and resembles smectic phases of thermotropic liquid crystals observed with small molecules. 相似文献
913.
Brain-derived neurotrophic factor prevents neuronal death in vivo 总被引:32,自引:0,他引:32
Developing vertebrate neurons are thought to depend for their survival on specific neurotrophic proteins present in their target fields. The limited availability of these proteins does not allow the survival of all neurons initially innervating a target, resulting in the widely observed phenomenon of naturally occurring neuronal death. Although a variety of proteins have been reported to promote the survival of neurons in tissue culture, the demonstration that these proteins increase neuronal numbers and/or decrease neuronal death in vivo has only been possible with nerve growth factor (NGF). The generalization of the concept that neurotrophic proteins regulate neuronal survival during normal development critically depends on the demonstration that the survival of neurons in vivo can be increased by the administration of a neurotrophic protein different from NGF. We report here that this is the case with brain-derived neurotrophic factor, a protein of extremely low abundance purified from the central nervous system. 相似文献
914.
Incubation periods for paediatric AIDS patients 总被引:11,自引:0,他引:11
I Auger P Thomas V De Gruttola D Morse D Moore R Williams B Truman C E Lawrence 《Nature》1988,336(6199):575-577
A recent seroprevalence study of newborns indicates that one in 62 children born in New York City has antibodies to the human immunodeficiency virus (HIV). The distribution of incubation periods for paediatric patients is needed to estimate future AIDS case loads from these seroprevalence data. Current estimates of incubation periods for paediatric patients are based on limited data. We use parametric and non-parametric methods to analyse incubation periods for 215 paediatric patients with AIDS whose only known route of infection is maternal. We conclude that incubation periods are longer than previously reported; that there is a distinct knee in the incubation period distribution at seven months which suggests two risk populations; and that there is an increase in incidence which is consistent with exponential growth. 相似文献
915.
Patients with lesions in the medial temporal lobe (MTL) of the brain, which includes the hippocampus, amygdala and parahippocampal gyrus, are severely impaired in their ability to remember and recognize words or faces which they saw only a short time ago. These lesions also prevent the effect of word repetition on cortical event-related potentials that are associated with these tasks. We have been able to study the response of individual neurons in the human medial temporal lobe to such delayed recognition tasks in epileptic patients undergoing neurosurgery. We found that some MTL neurons preferentially fired on sight of one particular word from a set of ten words used in a memory task, and others fired in response to one particular face. This stimulus-specific firing was maximal during the time that the neocortical event potentials are most sensitive to stimulus repetition, suggesting that the MTL contributes specific information to the cortex during the retrieval of recent memories. 相似文献
916.
Identity of the 19S 'prosome' particle with the large multifunctional protease complex of mammalian cells (the proteasome) 总被引:36,自引:0,他引:36
There have been many reports that eukaryotic cells contain ring-shaped 19S or 20S particles which are composed of numerous polypeptide subunits ranging in size between 25 and 35 kilodaltons. Because these particles seemed to copurify with inactive mRNA, they were assumed to function in regulating mRNA translation and hence were named 'prosomes' (for 'programmed-o-some'). A number of properties have been reported for these structures, including an association with specific RNA species or with certain heat-shock proteins and involvement in tRNA processing or aminoacyl tRNA synthesis. However, these proposed activities have not been supported by definitive evidence. During studies of the proteolytic systems in mammalian tissues, we noted many similarities between these 19S particles and the high molecular weight protease complexes that are present in most or all eukaryotic cells. This (700 kilodalton) enzyme complex, designated here as LAMP for 'large alkaline multi-functional protease', contains three distinct endoproteolytic sites which function at neutral or alkaline pH and are specific for hydrolysis of proteins, hydrophobic peptides, or basic peptides. This protease also exists in a latent form which can be activated by polylysine, fatty acids, or ATP. In this report, we show that the prosomes and these protease complexes are very similar or identical with respect to their size, polypeptide composition, immunological cross-reactivity, appearance in the electron microscope, radial symmetry of subunits, subcellular localization, and proteolytic activities. Therefore, the 'prosome' probably plays a critical role in intracellular protein breakdown, and we propose that it be renamed 'proteasome'. 相似文献
917.
Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation 总被引:22,自引:0,他引:22
In studying the functional role of an extracellular matrix proteoglycan, decorin, we have made observations that suggest a role for this proteoglycan in the control of cell proliferation. Extracellular matrices are made up of different combinations of collagens, elastin, hyaluronic acid, proteoglycans and various glycoproteins such as fibronectin. Most of these components can interact with cells, and much of the control of cell adhesion, migration and differentiation appears to be mediated by these interactions. Earlier studies have also attributed growth-regulatory activities to intact extracellular matrices, but the individual molecules responsible for these effects have not been characterized. We report here that Chinese hamster ovary (CHO) cell lines expressing human decorin from a stably transfected complementary DNA construct form a more orderly monolayer and grow to a lower saturation density than control cells lacking decorin. The extent of the morphological changes correlates with the level of decorin expression, and the saturation density is inversely proportional to it. The reduction in the saturation densities of the cell lines with the highest expression of decorin is more than 50%. These results reveal a novel growth inhibitory mechanism which may be related to contact inhibition of cell proliferation. 相似文献
918.
B E Saether 《Nature》1988,331(6157):616-617
A large amount of variation is found in most reproductive traits of birds. Clutch size for instance, can vary from 1 to 15 between species of similar body weight. The adaptive significance of this variation is only poorly understood. According to life-history theory, large clutch size and early onset of reproduction are expected when the chances of survival are low. There is some support for the existence of such a relationship from studies of single species. Here I present evidence that, in European birds, clutch size is increased, and onset of reproduction occurs earlier in life, when the probability of survival is low. 相似文献
919.
Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA 总被引:7,自引:0,他引:7
One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism. 相似文献
920.
Noradrenaline (NA) regulates arterial smooth muscle tone and hence blood vessel diameter and blood flow. NA apparently increases tone by causing a calcium influx through the cell membrane. Two calcium influx pathways have been proposed: voltage-activated calcium channels and NA-activated calcium-permeable channels that are voltage-insensitive. Although voltage-activated calcium channels have been identified in arterial smooth muscle, voltage-insensitive calcium channels activated by NA have not. We show here that NA contractions of rabbit mesenteric arteries increase with depolarization. The increase parallels the elevation of open-state probability (P0) of single, voltage-dependent calcium channels. The action of noradrenaline can be explained by NA-activating voltage-dependent calcium channels, rather than by opening a second type of channel. We show directly that NA increases the open-state probability of single calcium channels. Thus, in the presence of NA, calcium entry through voltage-dependent calcium channels can regulate smooth muscle tone at physiological membrane potentials. These results may have relevance to pathophysiological conditions such as hypertension. 相似文献