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171.
Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge 总被引:3,自引:0,他引:3
Humphries SE; Talmud PJ; Cox C; Sutherland W; Mann J 《QJM : monthly journal of the Association of Physicians》1996,89(9):671-680
We examined the role of common genetic variation in determining the
consistency and magnitude of change in plasma total cholesterol (TC) levels
in response to two separate changes from a high-saturated (SFA) to a
low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of
free-living healthy men and women. Consistent responders were defined as
those whose mean difference in the change in TC was within one SD of the
mean for all participants, and the remainder were defined as variable
responders. DNA was obtained from 55 individuals and genotype determined at
the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T)
and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent
responders, the apoBSP24 allele was significantly more common than in the
17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No
other polymorphism showed a significant frequency difference between
groups. In the group as a whole, the correlation between the change in TC
level in response to the first and second dietary change was 0.28 (p =
0.05), but those with one or more apoB SP24 alleles and those with the
apoCIII genotype CC had a significantly higher correlation than those with
other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02
(NS), respectively). In the group as a whole, mean response left TC 10%
higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII
genotypes affected the magnitude of this response. However, individuals
with the LPL HindIII genotype H+ H+ had a significantly smaller change in
mean TC in response to diet than those with one or more H- allele (9.3% vs.
14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the
consistency of response to change in dietary fat content, while variation
at the LPL gene locus affects magnitude of response.
相似文献
172.
173.
Wierzbicki AS; Lumb PJ; Semra YK; Crook MA 《QJM : monthly journal of the Association of Physicians》1998,91(4):291-294
Lipid targets can be difficult to attain in familial hypercholesterolaemia.
To compare atorvastatin with simvastatin- fenofibrate and
simvastatin-cholestyramine therapy, we studied 54 patients with familial
hypercholesterolaemia over periods of 2-6 months on each therapeutic
regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/-
11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and
increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved
reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/-
38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL.
Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in
cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a
1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not
significantly better than simvastatin-fenofibrate in improving the LDL:HDL
ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%)
had side- effects: two discontinued atorvastatin due to side-effects; two
patients had rashes; six had myalgia and two had diarrhoea.
Gastrointestinal side-effects were described in 16 (30.1%) patients on
simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were
seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%)
a 30% or greater fall in HDL was observed, compared to five patients with
resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no
significant differences in liver or muscle biochemistry between the
regimens, but atorvastatin did raise transaminase and creatine kinase
concentrations significantly compared to pre-treatment values (p = 0.001).
Atorvastatin significantly improves the lipid profile in most patients
compared with other regimens. It has a comparable incidence of side-effects
to combination therapy regimens.
相似文献
174.
H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. II. H-2 D region control of H-7.1-specific stimulator function in mixed lymphocyte culture and susceptibility to lysis by H-7.1- specific cytotoxic cells 下载免费PDF全文
The relative immunogenicity of the H-7.1 alloantigen has been shown in a previous communication to be regulated by a gene in the D region of the mouse major histocompatibility (H-2) complex. The level of relative immunogenicity was inferred from survival times of H-7.1-incompatible skin grafts donated by donors with different H-2 haplotype origins of H-2D region genes. In this communication we report the results of an extension of these previous investigations into the possible role of H-2D region genes in controlling the capacity of H-7.1-incompatible lymphocytes to stimulate H-7.1-speciflc mixed lymphocyte culture proliferation and generation of cytotoxic effector cells. The results reported herein demonstrate that the H-2D genotype of H-7.1-incompatible stimulator cells determines the relative H-7.1-specific capacity of those lymphocytes to stimulate H-7.1-specific proliferation of in vivo primed responder T cells in secondary mixed lymphocyte culture. H-2D(b)-bearing, H-7.l-incompatible stimulators were significantly more effective in stimulating H-7.1-specific proliferation than H-2D(d)-bearing stimulators. As expected, H-2D(b), H-7.1-in-compatible stimulators were also more effective than H-2D(d) a stimulators in generating H-7.1- specific cytotoxic effector cells. Further, the susceptibility of (51)Cr- labeled, H-7.1-incompatible lymphoblast targets to H-7.1-specific lysis was similarly regulated by an H-2D gene. Reciprocal H-2 restriction (F(1) cells are capable of killing only the cells bearing the immunizing cell parental H-2 haplotype) observed by other investigators for cytolysis of non-H-2-incompatible targets was not observed. H-2D a-bearing, H-7.1- incompatible stimulators stimulated generation of cytotoxic effectors capable of detectably lysing H-2D(b) but not H-2D(a)-bearing, H-7.1- incompatible targets. The impact of these observations on the proposed models for H-2 restriction of non-H-2 histocompatibility antigen-specific cytolysis is discussed. 相似文献
175.
Gina L. O'Grady FRACP Monkol Lek PhD Shireen R. Lamande PhD Leigh Waddell PhD Emily C. Oates PhD Jaya Punetha MS Roula Ghaoui FRACP Sarah A. Sandaradura FRACP Heather Best BSc Simranpreet Kaur MPhil Mark Davis PhD Nigel G. Laing PhD Francesco Muntoni MD Eric Hoffman PhD Daniel G. MacArthur PhD Nigel F. Clarke PhD Sandra Cooper PhD Kathryn North MD 《Annals of neurology》2016,80(1):101-111
176.
Estimated rate of prostacyclin secretion into the circulation of normal man. 总被引:9,自引:10,他引:9 下载免费PDF全文
G A FitzGerald A R Brash P Falardeau J A Oates 《The Journal of clinical investigation》1981,68(5):1272-1276
The rate of secretion of prostacyclin (PGI2) into the circulation of normal man was estimated by measurement of the 2,3-dinor-6-keto-PGF1 alpha (D) and 15-keto-13,14-dihydro-2,3-dinor-6-keto-PGF1 alpha (KDD) urinary metabolites of PGI2. Subjects received 6-h intravenous infusions of vehicle alone and PGI2 at 0.1, 0.4, and 2.0 ng/kg per min in random order. The fractional elimination of the metabolites was independent of the rate of PGI2 infusion. 6.8 +/- 0.3% of the infused PGI2 appeared as D and 4.1 +/- 0.4% as KDD. The regression of infused PGI2 upon the quantities of the two metabolites excreted in excess of control values permitted estimation of the rate of entry of endogenous PGI2 into the circulation corresponding to a given quantity of metabolite excreted. Using the quantities excreted in the 24 h from commencement of the infusions the estimated rates were 0.08 +/- 0.02 ng/kg per min from D and 0.10 +/- 0.03 from KDD. Studies with exogenous PGI2 suggest that infusion rates 2--4 ng/kg per min are required to achieve the threshold for inhibition of platelet function (ex vivo) in man. Although not precluding a role for PGI2 in local platelet-vessel wall interactions, the much lower estimates obtained in this study suggest that endogenous PGI2 is unlikely to act as a circulating antiplatelet agent in healthy man. 相似文献
177.
N S Oates S G Ball C M Perkins M R Lee 《Clinical science (London, England : 1979)》1979,56(3):261-264
1. Plasma and urine free dopamine were measured daily for 5 days in six normal subjects maintained on a low sodium diet. The subjects were then given dietary supplements of sodium chloride for 5 days and the measurements repeated. 2. Throughout the experiment the 24 h free dopamine excretion rates for all the subjects were higher than could be accounted for by renal clearance. Dopamine excretion increased significantly in response to the added sodium chloride whereas plasma dopamine remained unchanged. The rise in dopamine excretion preceded that of sodium excretion. 3. It is concluded that free dopamine is formed within the kidney in response to increased dietary sodium and may have a role in the control of sodium excretion. 相似文献
178.
Duplex ultrasound evaluation of normal native kidneys and native kidneys with urinary tract obstruction 总被引:1,自引:0,他引:1
The average resistive indices of 15 native kidneys from 8 patients with no known renal dysfunction were determined with the Doppler waveform obtained from the interlobar arteries. The average resistive index for this group was .58; the highest value was .66. The interlobar arteries of four native kidneys with urinary tract obstruction as well as those of the contralateral unobstructed kidneys were evaluated by Duplex ultrasound. Unilateral urinary tract obstruction was due to a congenital ureteropelvic junction obstruction in one patient or an acutely obstructing calculus at the ureterovesical junction in three patients. The average resistive index of the four obstructed kidneys was .75 and the lowest value was .71. The average resistive index of the four contralateral unobstructed kidneys in these patients and the 15 kidneys from patients with no known renal abnormalities was .58, which was significantly different from the value for the obstructed kidneys (p less than .005). The resistive index from the interlobar arteries of normal native kidneys is reproducible as previously reported in renal transplants. Pathologic renal processes, such as urinary tract obstruction, may be characterized by abnormally high resistive indices. 相似文献
179.
OSTLERE L; WARNER T; MEUNIER PJ; HULME P; HESP R; WATTS RWE; REEVE J 《QJM : monthly journal of the Association of Physicians》1991,79(3):503-515
Two patients with Type 1 (adult) Gaucher's disease and majorskeletal involvement with multiple fractures have been treatedwith the second generation bisphosphonate pamidronate for extensiveperiods. There was evidence of an immediate reduction in boneresorption, with increased calcium absorption (delayed in Patient1), improved calcium balance and maintained or improved bonedensity indices in the axial and peripheral skeleton. Therewas no evidence of immediate relapse on treatment cessation.No toxic effects of pamidronate treatment were identified andsubjective skeletal pain diminished in both patients. Histomorphometryof transiliac bone biopsies obtained before the start of treatment,after double in vivo tetracycline labelling, represents oneof the earliest reports of the quantitative findings in iliacbone invaded by Gaucher cells. 相似文献
180.
FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo 总被引:5,自引:0,他引:5
van Vugt MJ; Heijnen AF; Capel PJ; Park SY; Ra C; Saito T; Verbeek JS; van de Winkel JG 《Blood》1996,87(9):3593-3599
Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface- expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA- IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo. 相似文献