全文获取类型
收费全文 | 102421篇 |
免费 | 9347篇 |
国内免费 | 977篇 |
出版年
2023年 | 482篇 |
2022年 | 1098篇 |
2021年 | 2104篇 |
2020年 | 1274篇 |
2019年 | 1644篇 |
2018年 | 1890篇 |
2017年 | 1690篇 |
2016年 | 2646篇 |
2015年 | 4434篇 |
2014年 | 5041篇 |
2013年 | 5866篇 |
2012年 | 7758篇 |
2011年 | 7426篇 |
2010年 | 4763篇 |
2009年 | 4455篇 |
2008年 | 6174篇 |
2007年 | 6126篇 |
2006年 | 5712篇 |
2005年 | 5528篇 |
2004年 | 5320篇 |
2003年 | 5095篇 |
2002年 | 4790篇 |
2001年 | 1048篇 |
2000年 | 797篇 |
1999年 | 1075篇 |
1998年 | 1338篇 |
1997年 | 925篇 |
1996年 | 836篇 |
1995年 | 798篇 |
1994年 | 685篇 |
1993年 | 761篇 |
1992年 | 716篇 |
1991年 | 602篇 |
1990年 | 608篇 |
1989年 | 586篇 |
1988年 | 531篇 |
1987年 | 499篇 |
1986年 | 462篇 |
1985年 | 633篇 |
1984年 | 702篇 |
1983年 | 634篇 |
1982年 | 729篇 |
1981年 | 666篇 |
1980年 | 673篇 |
1979年 | 395篇 |
1978年 | 472篇 |
1977年 | 405篇 |
1976年 | 403篇 |
1974年 | 355篇 |
1973年 | 353篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
Summary Microbodies are ubiquitous organelles in fungal cells, occurring in both vegetative hyphae and spores. They are bounded by a single membrane and may contain a crystalloid inclusion with subunits spaced at regular intervals. Typically, they contain catalase which reacts with the cytochemical stain 3,3-diaminobenzidine to yield an electron-opaque product, urate oxidase,l--hydroxy acid oxidase andd-amino acid oxidase. Their fragility and the necessity to disrupt the tough fungal cell wall before isolating them make them difficult to isolate. Analysis of enzymes in purified or partially purified microbodies from fungi indicates that they participate in fatty acid degradation, the glyoxylate cycle, purine metabolism, methanol oxidation, assimilation of nitrogenous compounds, amine metabolism and oxalate synthesis. In organisms where microbodies are known to contain enzymes of the glyoxylate cycle, they are known as glyoxysomes; where they are known to contain peroxidatic activity, they are known as peroxisomes. In some cases microbodies contain enzymes for only a portion of a pathway or cycle. Thus, they must be involved in metabolic cooperation with other organelles, particularly mitochondria. The number, size and shape of microbodies in cells, their buoyant density and their enzyme contents may vary with the composition of the medium; their proliferation in cells is regulated by the growth environment. The isolation from the same organism of microbodies with different buoyant densities and different enzymes suggests strongly that more than one type of microbody can be formed by fungi. 相似文献
972.
Ana M. Moura-da-Silva R. David G. Theakston Julian M. Cramptonl 《Journal of molecular evolution》1996,43(3):263-269
The evolution of the Metalloproteinase Disintegrin Cysteine-rich (MDC) gene family and that of the mammalian Matrix-degrading
Metalloproteinases (MMPs) are compared. The alignment of snake venom and mammalian MDC and MMP precursor sequences generated
a phylogenetic tree that grouped these proteins mainly according to their function. Based on this observation, a common ancestry
is suggested for mammalian and snake venom MDCs; it is also possible that gene duplication of the already-assembled domain
structure, followed by divergence of the copies, may have significantly contributed to the evolution of the functionally diverse
MDC proteins. The data also suggest that the structural resemblance of the zinc-binding motif of venom MDCs and MMPs may best
be explained by common ancestry and conservation of the proteolytic motifs during the divergence of the proteins rather than
through convergent evolution.
Correspondence to: J.M. Crampton 相似文献
973.
Selection at linked sites has important consequences for the properties of neutral variation and for tests of the predictions
of the neutral theory of molecular evolution. We review the theory of the effect of adaptive gene substitutions on neutral
variability at linked sites (hitchhiking or selective sweeps) and discuss theoretical results on the effect of selection against
deleterious alleles on variation at linked sites (background selection). InDrosophila melanogaster there is a clear relation between the frequency of recombination in a given region of the chromosome and the amount of natural
variability in that region. Attempts to predict this relation have given rise to models of selective sweeps and background
selection. We describe possible methods of discriminating between these models, and also discuss the probable strong influence
of selective sweeps on variation in largely nonrecombining genomes, with particular reference toEscherichia coll. Finally we present some unresolved questions and possible directions for future research. 相似文献
974.
Einat Sadot David Gurwitz Jacob Barg Leah Behar Irith Ginzburg †Abraham Fisher 《Journal of neurochemistry》1996,66(2):877-880
Abstract: Hyperphosphorylated τ proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that τ phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m1 muscarinic acetylcholine receptor. Stimulation of m1 receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased τ phosphorylation, as indicated by specific τ monoclonal antibodies that recognize phosphorylation-dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on τ phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of τ microtubule-associated protein. 相似文献
975.
Angela Clements David Allsop Dominic M. Walsh Carvell H. Williams 《Journal of neurochemistry》1996,66(2):740-747
Abstract: The fibrillogenic properties of Alzheimer's Aβ peptides corresponding to residues 1–40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37°C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal Aβ, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to β sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20× the concentration of Zn2+, Cu2+ displaced >95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 µM was obtained for the binding of Zn2+ to Aβ but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon. 相似文献
976.
Abstract: S -Adenosylmethionine is an essential ubiquitous metabolite central to many biochemical pathways, including transmethylation and polyamine biosynthesis. Reduced CSF S -adenosylmethionine levels in Alzheimer's disease have been reported; however, no information is available regarding the status of S -adenosylmethionine or S -adenosylmethionine-dependent methylation in the brain of patients with this disorder. S -Adenosylmethionine concentrations were measured in postmortem brain of 11 patients with Alzheimer's disease. We found decreased levels of S -adenosylmethionine (−67 to −85%) and its demethylated product S -adenosylhomocysteine (−56 to −79%) in all brain areas examined (cerebral cortical subdivisions, hippocampus, and putamen) as compared with matched controls (n = 14). S -Adenosylmethionine and S -adenosylhomocysteine levels were normal in occipital cortex of patients with idiopathic Parkinson's disease (n = 10), suggesting that the decreased S -adenosylmethionine levels in Alzheimer's disease are not simply a consequence of a chronic, neurodegenerative condition. Reduced S -adenosylmethionine levels could be due to excessive utilization in polyamine biosynthesis. The severe reduction in levels of this essential biochemical substrate would be expected to compromise seriously metabolism and brain function in patients with Alzheimer's disease and may provide the basis for the observations of improved cognition in some Alzheimer's patients following S -adenosylmethionine therapy. 相似文献
977.
Mark A. Batzer Santosh S. Arcot Joshua W. Phinney Michelle Alegria-Hartman David H. Kass Stephen M. Milligan Colin Kimpton Peter Gill Manfred Hochmeister Panayiotis A. Ioannou Rene J. Herrera Donald A. Boudreau W. Douglas Scheer Bronya J. B. Keats Prescott L. Deininger Mark Stoneking 《Journal of molecular evolution》1996,42(1):22-29
The Alu family of intersperesed repeats is comprised of ovr 500,000 members which may be divided into discrete subfamilies based upon mutations held in common between members. Distinct subfamilies of Alu sequences have amplified within the human genome in recent evolutionary history. Several individual Alu family members have amplified so recently in human evolution that they are variable as to presence and absence at specific loci within different human populations. Here, we report on the distribution of six polymorphic Alu insetions in a survey of 563 individuals from 14 human population groups across several continents. Our results indicate that these polymorphic Alu insertions probably have an African origin and that there is a much smaller amount of genetic variation between European populations than that found between other populations groups.
Present address: Department of Pathology, Stanley S. Scott Cancer Center, Louisiana State University Medical Center, 1901 Perdido St., New Orleans, LA 70112
Correspondence to: M.A. Batzer 相似文献
978.
Functional Expression of P-Glycoprotein in an Immortalised Cell Line of Rat Brain Endothelial Cells, RBE4 总被引:5,自引:3,他引:2
David J. Begley Delphine Lechardeur Zheng-Duan Chen Christopher Rollinson †Michèle Bardoul †Françoise Roux Daniel Scherman N. Joan Abbott 《Journal of neurochemistry》1996,67(3):988-995
Abstract: The presence of P-glycoprotein in the cell plasma membrane limits the penetration of many cytotoxic substances into cells that express the gene product. There is considerable evidence also to indicate that P-glycoprotein is expressed as part of the normal blood-brain barrier in the luminal membranes of the cerebral capillary endothelial cells, where it presumably performs a protective function for the brain. This report describes the functional expression of P-glycoprotein in an immortalised cell line, RBE4, derived from rat cerebral capillary endothelial cells. The expression of P-glycoprotein is demonstrated by western immunoblotting and by immunogold and fluorescent staining with monoclonal antibodies. The cellular accumulation of [3 H]colchicine and [3 H]vinblastine is investigated and shown to be enhanced by the presence of azidothymidine, chlorpromazine, verapamil, cyclosporin A, and PSC 833 ([3'-keto-Bmt1 ]-[Val2 ]-cyclosporin) at 50 or 100 µ M concentration. It is concluded that the RBE4 cell line is a valuable tool for investigating the mechanisms of P-glycoprotein activity both in the blood-brain barrier and in multidrug resistance in general. 相似文献
979.
Abstract: A readily soluble 5'-nucleotidase was purified 1,800-fold from rat brain 105,000- g supernatant. The enzyme showed similarity to the 5'-nucleotidase ectoenzyme of plasma membranes. It exhibited a low K m for AMP, which was preferred over IMP as substrate. It was inhibited by free ATP and ADP and by α,β-methylene ADP. The enzyme appeared to be a glycoprotein on the basis of its interaction with concanavalin A. It contained a phosphatidylinositol moiety because treatment with phosphatidylinositol-specific phospholipase C increased its hydrophilicity. A single subunit of Mr = 54,300 ± 800 was observed, which is appreciably smaller than published values for the 5'-nucleotidase ectoenzyme or for other low- K m "soluble" 5'-nucleotidases. The soluble 5'-nucleotidase showed an elution profile on AMP-Sepharose affinity chromatography or on Mono Q ion-exchange chromatography different from that of the brain ectoenzyme. Forty-two percent of the soluble 5'-nucleotidase in brain 105,000- g supernatant did not bind to a Mono Q ion-exchange column because of its interaction with a soluble factor. This factor could be removed by chromatography on concanavalin A-Sepharose. The factor had the novel property of increasing the sensitivity of the purified soluble 5'-nucleotidase toward the inhibitor ATP by 20-fold. This factor was also able to increase the inhibition of brain 5'-nucleotidase ectoenzyme by ATP. 相似文献
980.