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991.
A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors 总被引:98,自引:0,他引:98
P Ponte P Gonzalez-DeWhitt J Schilling J Miller D Hsu B Greenberg K Davis W Wallace I Lieberburg F Fuller 《Nature》1988,331(6156):525-527
The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease. 相似文献
992.
Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II 总被引:122,自引:0,他引:122
Ribosomal protein S6 is a component of the eukaryotic 40S ribosomal subunit that becomes phosphorylated on multiple serine residues in response to a variety of mitogens, including insulin, growth factors, and transforming proteins of many oncogenic viruses. Recently, an activated S6 kinase (S6 K II) has been purified to homogeneity from Xenopus eggs, and characterized immunologically and at the molecular level. Purified S6 K II can be deactivated in vitro by incubation with either protein phosphatase 1 or protein phosphatase 2A. Reactivation and phosphorylation of S6 K II occurs in vitro with an insulin-stimulated microtubule-associated protein-2 (MAP-2) protein kinase which is itself a phosphoprotein that can be deactivated by protein phosphatase 2A. These studies suggest that a step in insulin signalling involves sequential activation by phosphorylation of at least two serine/threonine protein kinases. 相似文献
993.
Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease 总被引:104,自引:0,他引:104
R E Tanzi A I McClatchey E D Lamperti L Villa-Komaroff J F Gusella R L Neve 《Nature》1988,331(6156):528-530
Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA. 相似文献
994.
995.
996.
Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms 总被引:85,自引:0,他引:85
A H Paterson E S Lander J D Hewitt S Peterson S E Lincoln S D Tanksley 《Nature》1988,335(6192):721-726
The conflict between the Mendelian theory of particulate inheritance and the observation of continuous variation for most traits in nature was resolved in the early 1900s by the concept that quantitative traits can result from segregation of multiple genes, modified by environmental effects. Although pioneering experiments showed that linkage could occasionally be detected to such quantitative trait loci (QTLs), accurate and systematic mapping of QTLs has not been possible because the inheritance of an entire genome could not be studied with genetic markers. The use of restriction fragment length polymorphisms (RFLPs) has made such investigations possible, at least in principle. Here, we report the first use of a complete RFLP linkage map to resolve quantitative traits into discrete Mendelian factors, in an interspecific back-cross of tomato. Applying new analytical methods, we mapped at least six QTLs controlling fruit mass, four QTLs for the concentration of soluble solids and five QTLs for fruit pH. This approach is broadly applicable to the genetic dissection of quantitative inheritance of physiological, morphological and behavioural traits in any higher plant or animal. 相似文献
997.
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
998.
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
999.
Visual search for a conjunction of movement and form is parallel 总被引:7,自引:0,他引:7
Treisman has proposed when a human subject performs a visual search, the search is parallel for targets defined by a single feature, and serial for targets defined by a conjunction of features. Here we report that this is not true for targets defined by a conjunction of the features movement and form. Detection of a moving X among randomly distributed moving Os and static Xs is parallel. Search is uninfluenced by the stationary stimuli despite their spatial intermingling with the moving items. Thus, attention can be restricted to a spatially dispersed perceptual group, defined by common movement. This contradicts previous conclusions from visual search experiments that attention can only be assigned to contiguous regions of visual space. The search process first segregates the array into moving and stationary items, and then examines the moving group for the target form. Cells in the middle temporal region (cortical area MT) have the properties required to perform these operations. 相似文献
1000.
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