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991.
The Tomlinson report''s emphasis on primary care and its essentially quantitative analysis of hospital care in London leaves little space for a picture of how secondary care for Londoners should look. In this article Fiona Moss and Martin McNicol argue that most outpatient work does not need to be done in hospitals. With proper organisation and better premises a genuinely specialist consultative service can be provided in primary health care centres, with benefit to patients and communication between primary and secondary care doctors. Hospitals would then house those outpatient services that needed major investigative facilities and much reduced inpatient capacity. It may no longer be necessary for each acute unit to offer a full range of services. Such a pattern of secondary care will have implications for the organisation of accident and emergency services and for postgraduate training. Above all Moss and McNicol argue that Tomlinson''s recommendations demand that general practitioners and specialists should re-examine the services hospitals provide and agree on the best settings for different sorts of health care and the most appropriate skills to provide it. 相似文献
992.
Characterization of a vaccinia virus-encoded 42-kilodalton class I membrane glycoprotein component of the extracellular virus envelope.
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Using a reverse genetic approach, we have demonstrated that the product of the B5R open reading frame (ORF), which has homology with members of the family of complement control proteins, is a membrane glycoprotein present in the extracellular enveloped (EEV) form of vaccinia virus but absent from the intracellular naked (INV) form. An antibody (C'-B5R) raised to a 15-amino-acid peptide from the translated B5R ORF reacted with a 42-kDa protein (gp42) found in vaccinia virus-infected cells and cesium chloride-banded EEV but not INV. Under nonreducing conditions, an 85-kDa component, possibly representing a hetero- or homodimeric form of gp42, was detected by both immunoprecipitation and Western immunoblot analysis. Metabolic labeling with [3H]glucosamine and [3H]palmitate revealed that the B5R product is glycosylated and acylated. The C-terminal transmembrane domain of the protein was identified by constructing a recombinant vaccinia virus that overexpressed a truncated, secreted form of the B5R ORF product. By N-terminal sequence analysis of this secreted protein, the site of signal peptide cleavage of gp42 was determined. A previously described monoclonal antibody (MAb 20) raised to EEV, which immunoprecipitated a protein with biochemical characteristics similar to those of wild-type gp42, reacted with the recombinant, secreted product of the B5R ORF. Immunofluorescence of wild-type vaccinia virus-infected cells by using either MAb 20 or C'-B5R revealed that the protein is expressed on the cell surface and within the cytoplasm. Immunogold labeling of EEV and INV with MAb 20 demonstrated that the protein was found exclusively on the EEV membrane. 相似文献
993.
J Moss P A Watkins S J Stanley M R Purnell W R Kidwell 《The Journal of biological chemistry》1984,259(8):5100-5104
Glutamine synthetase from ovine brain has a critical arginine residue at the catalytic site (Powers, S. G., and Riordan, J.F. (1975) Proc. Natl. Acad. Sci. U.S. A. 72, 2616-2620). This enzyme is now shown to be a substrate for a purified NAD:arginine ADP-ribosyltransferase from turkey erythrocyte cytosol that catalyzes the transfer of ADP-ribose from NAD to arginine and purified proteins. The transferase catalyzed the inactivation of the synthetase in an NAD-dependent reaction; ADP-ribose and nicotinamide did not substitute for NAD. Agmatine, an alternate ADP-ribose acceptor in the transferase-catalyzed reaction, prevented inactivation of glutamine synthetase. MgATP, a substrate for the synthetase which was previously shown to protect that enzyme from chemical inactivation, also decreased the rate of inactivation in the presence of NAD and ADP-ribosyltransferase. Using [32P]NAD, it was observed that approximately 90% inactivation occurred following the transfer of 0.89 mol of [32P]ADP-ribose/mol of synthetase. The erythrocyte transferase also catalyzed the NAD-dependent inactivation of glutamine synthetase purified from chicken heart; 0.60 mol of ADP-ribose was transferred per mol of enzyme, resulting in a 95% inactivation. As noted with the ovine brain enzyme, agmatine and MgATP protected the chicken synthetase from inactivation and decreased the extent of [32P]ADP-ribosylation of the synthetase. These observations are consistent with the conclusion that the NAD:arginine ADP-ribosyltransferase modifies specifically an arginine residue involved in the catalytic site of glutamine synthetase. Although the transferase can use numerous proteins as ADP-ribose acceptors, some characteristics of this particular arginine, perhaps the same characteristics that are involved in its function in the catalytic site, make it a favored ADP-ribose acceptor site for the transferase. 相似文献
994.
995.
996.
An investigation of the hemoglobin levels of infants in potentially high-risk categories demonstrated the possibilities of a public health program of screening and referral for anemia. Blood samples for hemoglobin determinations and particulars of 24-hour dietary intakes were obtained for 252 infants between the ages of 6 and 18 months at seven child health centres in the City of Toronto. Twenty-nine percent of the infants had hemoglobin levels below 10 g./100 ml. of blood. Problems in the collection and analysis of dietary data limited the interpretation of iron intakes. 相似文献
997.
Type 5 acid phosphatase. Sequence, expression and chromosomal localization of a differentiation-associated protein of the human macrophage 总被引:4,自引:0,他引:4
D K Lord N C Cross M A Bevilacqua S H Rider P A Gorman A V Groves D W Moss D Sheer T M Cox 《European journal of biochemistry》1990,189(2):287-293
The purple acid phosphatases and uteroferrin belong to a diverse multifunctional class of binuclear iron-containing proteins that includes haemerythrin and ribonucleotide reductase. In the pig, uteroferrin has been implicated in the delivery of iron to the foetus, but the role of the related human type 5 acid phosphatase that is principally found in resident tissue macrophages is not yet clear. To define further the function of this metalloenzyme, we have isolated and sequenced a cDNA clone for type 5 acid phosphatase and investigated expression of its gene in human tissues. The phosphatase clone contains an open reading frame of 975 bp and encodes a protein of 325 amino acids, including a signal peptide of 19 residues and two potential sites for N-glycosylation. The type 5 acid phosphatase gene mapped to the short arm of human chromosome 19 and was found to have a restriction fragment length polymorphism on digestion with XbaI. Expression of phosphatase mRNA was restricted to mononuclear phagocytes and the enzyme was induced greater than 20-fold on transformation of normal human monocytes to macrophages by culture in serum-supplemented medium. Type 5 acid phosphatase thus represents a tightly regulated system for the study of molecular events in the differentiation programme of the normal macrophage. 相似文献
998.
We have measured the magnetic susceptibility in the temperature range 1.4–77°K of three derivatives of bovine superoxide dismutase in which Co2+ was substituted for Zn2+: (1) 2Co2+ — in which Co2+ binds to the normal Zn2+ site and the Cu2+ site is unoccupied, (2) 2Co2+2Cu2+ — in which the Zn2+ site is occupied by Co2+ and the copper sites contains Cu2+ and (3) 2Co2+2Cu+ — which is the reduced form of the second derivative. The 2Co2+ protein exhibits Curie paramagnetism indicating and the zero-field splitting must be greater than ?20 cm?1. The same propeties have been observed with the 2Co2+2Cu+-protein. By contrast, the 2Co2+2Cu2+-derivative exhibits relatively little paramagnetism, some of which arises from non-specifically associated metal ions. The lower susceptibility is due to antiferromagnetic coupling between Co2+ and Cu2+, and the magnitude of the coupling constant is probably ?5 cm?1. 相似文献
999.
Tamas S. Yelland Claire E. Naylor Tannya Bagoban Christos G. Savva David S. Moss Bruce A. McClane Ingolf E. Blasig M. Popoff Ajit K. Basak 《Journal of molecular biology》2014
CPE (Clostridium perfringens enterotoxin) is the major virulence determinant for C. perfringens type-A food poisoning, the second most common bacterial food-borne illness in the UK and USA. After binding to its receptors, which include particular human claudins, the toxin forms pores in the cell membrane. The mature pore apparently contains a hexamer of CPE, claudin and, possibly, occludin. The combination of high binding specificity with cytotoxicity has resulted in CPE being investigated, with some success, as a targeted cytotoxic agent for oncotherapy. In this paper, we present the X-ray crystallographic structure of CPE in complex with a peptide derived from extracellular loop 2 of a modified, CPE-binding Claudin-2, together with high-resolution native and pore-formation mutant structures. Our structure provides the first atomic-resolution data on any part of a claudin molecule and reveals that claudin's CPE-binding fingerprint (NPLVP) is in a tight turn conformation and binds, as expected, in CPE's C-terminal claudin-binding groove. The leucine and valine residues insert into the binding groove while the first residue, asparagine, tethers the peptide via an interaction with CPE's aspartate 225 and the two prolines are required to maintain the tight turn conformation. Understanding the structural basis of the contribution these residues make to binding will aid in engineering CPE to target tumor cells. 相似文献
1000.
Kristopher T Kahle Nancy D Merner Perrine Friedel Liliya Silayeva Bo Liang Arjun Khanna Yuze Shang Pamela Lachance‐Touchette Cynthia Bourassa Annie Levert Patrick A Dion Brian Walcott Dan Spiegelman Alexandre Dionne‐Laporte Alan Hodgkinson Philip Awadalla Hamid Nikbakht Jacek Majewski Patrick Cossette Tarek Z Deeb Stephen J Moss Igor Medina Guy A Rouleau 《EMBO reports》2014,15(7):766-774
The KCC2 cotransporter establishes the low neuronal Cl− levels required for GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability. However, no mutations in KCC2 have been documented in human disease. Here, we report two non-synonymous functional variants in human KCC2, R952H and R1049C, exhibiting clear statistical association with idiopathic generalized epilepsy (IGE). These variants reside in conserved residues in the KCC2 cytoplasmic C-terminus, exhibit significantly impaired Cl−-extrusion capacities resulting in less hyperpolarized Gly equilibrium potentials (EGly), and impair KCC2 stimulatory phosphorylation at serine 940, a key regulatory site. These data describe a novel KCC2 variant significantly associated with a human disease and suggest genetically encoded impairment of KCC2 functional regulation may be a risk factor for the development of human IGE. 相似文献