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21.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
22.
Human immune response to outer membrane protein CD of Moraxella catarrhalis in adults with chronic obstructive pulmonary disease 下载免费PDF全文
Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD. 相似文献
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24.
L. Zller J. Scholz R. Stohwasser L. B. Giebel K. K. Sethi E. K. F. Bautz G. Darai 《Journal of medical virology》1989,27(3):231-237
Sera from patients with nephropathia epidemica (NE) or Korean hemorrhagic fever (KHF) were tested for specific antibody response to antigens of H?lln?s virus and Hantaan virus strain 76-118. A Vero E6 derived cell line persistently infected with H?lln?s virus strain B1, and Vero E6 cells freshly infected with Hantaan virus type strain 76-118 were used as antigens in the immunofluorescence assay (IFA) and the immunoblot. Blots were prepared from whole cell lysates. The convalescent-phase sera of NE patients tested in this study regularly revealed a marked reaction with a 52 kilodalton (Kd) protein of H?lln?s virus and a 50 Kd protein of Hantaan virus. A convalescent serum from a patient with Korean hemorrhagic fever and a rat antiserum against Hantaan virus could recognize the 50 Kd band of Hantaan virus but showed no apparent reactivity with the 52 Kd component of H?lln?s virus in the standard dilutions. Some sera could additionally identify minor bands in the 55 Kd and/or 67 Kd region of the blots. A one-way cross reactivity between Hantaan and H?lln?s viruses was also evident from the results of the immunofluorescence assays in that NE convalescent sera reacted with both viruses, whereas KHF convalescent or anti-Hantaan sera gave strongly positive results with Hantaan virus but only faint reaction with H?lln?s virus. 相似文献
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26.
This paper constructs a unified framework to survey most of the work done to date on decision 1 decision horizon replaces the term planning horizon used in the literature in the context of this paper. This is done because of an alternate and more popular use of the term planning horizon as simply the given length of the horizon in a finite horizon problem. and forecast horizons in a stochastic environment. The paper is divided into sections by type of model. For each model type, the issues of existence of these horizons and of derivation of sufficient conditions for their determination are studied. Appropriate examples are presented. 相似文献
27.
Don V. Jackson Jr. V. Sagar Sethi Tony R. Long Hyman B. Muss Charles L. Spurr 《Cancer chemotherapy and pharmacology》1984,13(2):114-119
Summary The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m2 bolus injection, 1.2 mg/m2/day infusion for 5 days, or 2.0 mg/m2/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5×10-7 M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t1/2 15.0±9.4 h). Compared with bolus injection, 1.2-to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m2 and 1.2 mg/m2. Whereas steady-state concentrations (1×10-8 M) were maintained throughout the infusion of 1.2 mg/m2/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m2/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m2 infusion, but were somewhat more sustained in the 1.2-mg/m2 infusion group. The average urinary excretion was similar for each dose-schedule (8%–11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule. 相似文献
28.
29.
J G Copeland T B Icenogle R J Williams L J Rosado S M Butman M A Vasu G K Sethi A N McDonald E Klees M J Rhenman 《The Journal of thoracic and cardiovascular surgery》1990,99(5):852-860
Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T-cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation. 相似文献
30.
Voluntary gaze may evoke a number of neurological phenomena such as vertigo, tinnitus, blepharoclonus, eyelid nystagmus, "facial nystagmus," involuntary laughter, and seizures. We report two patients in whom eccentric gaze evoked facial twitching and arm movement. Electroencephalograms remained unchanged during these movements. The pathogenesis of these movements is unclear but may involve ephaptic transmission. 相似文献