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151.
152.
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
153.
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
154.
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
155.
156.
D K Hansen R E Billings 《The Journal of pharmacology and experimental therapeutics》1986,238(3):985-989
Exposure of pregnant rats to the anesthetic gas, nitrous oxide (N2O), has been reported to be teratogenic. This gas decreases activity of the enzyme 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase) and alters the level and distribution of folic acid derivatives in embryonic tissue. Because of their role in purine, thymidine and amino acid metabolism, alterations in the levels of various folate forms could affect macromolecular synthesis. The effect of N2O exposure on the number of somites, the content of DNA, RNA and protein as well as the incorporation of thymidine, deoxyuridine or serine into DNA were determined. Pregnant rats were exposed for 24 hr to 50% N2O-50% O2 beginning on day 10 of gestation. Control animals were exposed to 50% N2-50% O2. Embryos were removed and cultured for 4 hr using a rodent whole embryo culture system in medium containing radiolabeled precursors for DNA. Treatment with N2O had no effect on somite number, RNA or protein content. However, there was a significant decrease in DNA content. There was an increase in the incorporation of thymidine into DNA, but the incorporation of deoxyuridine and serine into DNA was decreased. These data demonstrate that treatment of pregnant rats with N2O results in decreased DNA synthesis and content in exposed embryos. 相似文献
157.
Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor 下载免费PDF全文
Zhang Q Mousdicas N Yi Q Al-Hassani M Billings SD Perkins SM Howard KM Ishii S Shimizu T Travers JB 《The Journal of clinical investigation》2005,115(10):2855-2861
Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis. 相似文献
158.
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
159.
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
160.
Sundstrom Beth Billings Deborah Smith Ellie Ferrara Merissa Albert Bill Suellentrop Katherine 《Maternal and child health journal》2019,23(8):1036-1047
Maternal and Child Health Journal - Introduction: In South Carolina, 50% of all pregnancies are unintended. Intrauterine devices (IUDs) and the implant are recommended as top-tier contraceptive... 相似文献