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471.
Dodatko T Fedorov AA Grynberg M Patskovsky Y Rozwarski DA Jaroszewski L Aronoff-Spencer E Kondraskina E Irving T Godzik A Almo SC 《Biochemistry》2004,43(33):10628-10641
Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed beta-helical fold present in C-CAP appears to support a wide range of biological functions. 相似文献
472.
From modulator to mediator: rapid effects of BDNF on ion channels 总被引:10,自引:0,他引:10
Rose CR Blum R Kafitz KW Kovalchuk Y Konnerth A 《BioEssays : news and reviews in molecular, cellular and developmental biology》2004,26(11):1185-1194
Neurotrophins (NTs) are {?AUTHOR} a family of structurally related, secreted proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. 1 , 2 Among these, BDNF (brain‐derived neurotrophic factor) has drawn considerable interest because both its synthesis and secretion are increased by physiological levels of activity, indicating a unique role of this neurotrophin in coupling neuronal activity to structural and functional properties of neuronal circuits. In addition to its classical neurotrophic effects, which are evident within hours or days and which usually result from changes in cellular gene expression, BDNF exerts acute effects on synaptic transmission and is involved in the induction of long‐term potentiation. Many of these rapid effects of BDNF are mediated by its modulation of ion channel properties following TrkB‐mediated activation of intracellular second messenger cascades and protein phosphorylation. However, recent reports have shown that BDNF not only acts as a modulator of ion channels, but can also directly and rapidly gate a Na+ channel, thereby assigning BDNF the properties of a classical excitatory transmitter. Thus, BDNF, in addition its role as a potent neuromodulator, emerges as an excitatory transmitter‐like substance which acutely controls resting membrane potential, neuronal excitability, synaptic transmission and participates in the induction of synaptic plasticity. BioEssays 26:1185–1194, 2004. © 2004 Wiley Periodicals, Inc. 相似文献
473.
Mokrov YG 《Radiation and environmental biophysics》2004,43(2):127-139
In 1951 and 1952 specialists from the Mayak production association investigated the radiological situation in the area of the Metlinski reservoir that was located 5-7 km from the site of liquid radioactive waste (LRW) discharge. Based on their measurements of both the specific radioactivity in the water and the dose-rate above the water surface, the gamma-field above the water surface in 1951 was demonstrated to be mainly due to (95)Zr+(95)Nb. The dose-rate at the shore of the reservoir was calculated for the period 1949-1951. In November and December 1951, the gamma-field at the shore was mainly due to (140)Ba+(140)La. For the period 1949-1951, the external exposure of the Metlino population due to the decay of these radionuclides was about 200 R (2 Sv), most of the dose having been produced in 1951. The contribution of (137)Cs to external doses did at that time probably not exceed a fraction of several percent. This finding is in contradiction to the assumptions made in the most recent TRDS-2000 system that was developed to reconstruct the doses to the residents of the Techa river. The results presented here demonstrate that the reconstruction of external doses received by the Metlino population as well as by the Techa river residents can be improved for the most critical period between 1949 and 1954. 相似文献
474.
Gottlöber P Steinert M Weiss M Bebeshko V Belyi D Nadejina N Stefani FH Wagemaker G Fliedner TM Peter RU 《Radiation research》2001,155(3):409-416
The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure. 相似文献
475.
476.
The concept of a prion as an infectious self-propagating protein isoform was initially proposed to explain certain mammalian diseases. It is now clear that yeast also has heritable elements transmitted via protein. Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-β aggregates (amyloids). Recently, there has been an explosion in the number of recognized prions in yeast. Yeast continues to lead the way in understanding cellular control of prion propagation, prion structure, mechanisms of de novo prion formation, specificity of prion transmission, and the biological roles of prions. This review summarizes what has been learned from yeast prions. 相似文献
477.
Balabanova LA Gafurov YM Pivkin MV Terentyeva NA Likhatskaya GN Rasskazov VA 《Marine biotechnology (New York, N.Y.)》2012,14(1):87-95
An extracellular nuclease was purified 165-fold with a specific activity of 41,250 U/mg poly(U) by chromatography with modified
chitosan from the culture of marine fungus Penicillium melinii isolated from colonial ascidium collected near Shikotan Island, Sea of Okhotsk, at a depth of 123 m. The purified nuclease
is a monomer with the molecular weight of 35 kDa. The enzyme exhibits maximum activity at pH 3.7 for DNA and RNA. The enzyme
is stable until 75°C and in the pH range of 2.5–8.0. The enzyme endonucleolytically degrades ssDNA and RNA by 3′–5′ mode to
produce 5′-oligonucleotides and 5′-mononucleotides; however, it preferentially degrades poly(U). The enzyme can digest dsDNA
in the presence of pregnancy-specific beta-1-glycoprotein-1. The nuclease acts on closed circular double-stranded DNA to produce
opened circular DNA and then the linear form DNA by single-strand scission. DNA sequence encoding the marine fungus P. melinii endonuclease revealed homology to S1-type nucleases. The tight correlation found between the extracellular endonuclease activity
and the rate of H3-thymidine uptake by actively growing P. melinii cells suggests that this nuclease is required for fulfilling the nucleotide pool of precursors of DNA biosynthesis during
the transformation of hyphae into the aerial mycelium and conidia in stressful environmental conditions. 相似文献
478.
Yulia N. Nekrasova Yury A. Zolotarev Elena V. Navolotskaya 《Journal of peptide science》2012,18(2):83-87
Two selective agonists of nonopioid β‐endorphin receptor, synthetic peptides TPLVTLFK (octarphin) and SLTCLVKGFY (immunorphin), were labeled with tritium to specific activity of 29 and 25 Ci/mmol, respectively. Both labeled peptides were found to bind to high‐affinity naloxone‐insensitive binding sites on the membranes isolated from the rat myocardium (Kd = 2.0 ± 0.2 and 2.5 ± 0.3 nM, respectively). The [3H]octarphin specific binding to the myocardial membranes was inhibited by unlabeled β‐endorphin (Ki = 1.9 ± 0.2 nM) and immunorphin (Ki = 2.2 ± 0.3 nM). The [3H]immunorphin specific binding with the membranes was inhibited by unlabeled β‐endorphin (Ki = 2.3 ± 0.3 nM) and octarphin (Ki = 2.4 ± 0.3 nM). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but also to α‐endorphin, γ‐endorphin, [Met5]enkephalin and [Leu5]enkephalin. Thus, β‐endorphin, immunorphin and octarphin bind to the common high‐affinity naloxone‐insensitive receptor of the rat myocardial membranes. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
479.
Gong H Romanova NV Allen KD Chandramowlishwaran P Gokhale K Newnam GP Mieczkowski P Sherman MY Chernoff YO 《PLoS genetics》2012,8(4):e1002634
Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington's disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates and cause cytotoxicity in yeast cells bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline(P)-rich region targets polyglutamines to the large perinuclear deposit (aggresome). Aggresome formation ameliorates polyglutamine cytotoxicity in cells containing only the prion form of Rnq1 protein. Here we show that expanded polyglutamines both with (poly-QP) or without (poly-Q) a P-rich stretch remain toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). A Sup35 derivative that lacks the QN-rich domain and is unable to be incorporated into aggregates counteracts cytotoxicity, suggesting that toxicity is due to Sup35 sequestration. Increase in the levels of another release factor, Sup45 (eRF1), due to either disomy by chromosome II containing the SUP45 gene or to introduction of the SUP45-bearing plasmid counteracts poly-Q or poly-QP toxicity in the presence of the Sup35 prion. Protein analysis confirms that polyglutamines alter aggregation patterns of Sup35 and promote aggregation of Sup45, while excess Sup45 counteracts these effects. Our data show that one and the same mode of polyglutamine aggregation could be cytoprotective or cytotoxic, depending on the composition of other aggregates in a eukaryotic cell, and demonstrate that other aggregates expand the range of proteins that are susceptible to sequestration by polyglutamines. 相似文献
480.
Thomas John Bender Matthew E. Wise Okey Utah Anne C. Moorman Umid Sharapov Jan Drobeniuc Yury Khudyakov Marielle Fricchione Mary Beth White-Comstock Nicola D. Thompson Priti R. Patel 《PloS one》2012,7(12)