全文获取类型
收费全文 | 2973篇 |
免费 | 252篇 |
国内免费 | 32篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 189篇 |
妇产科学 | 112篇 |
基础医学 | 366篇 |
口腔科学 | 80篇 |
临床医学 | 288篇 |
内科学 | 523篇 |
皮肤病学 | 65篇 |
神经病学 | 83篇 |
特种医学 | 408篇 |
外科学 | 486篇 |
综合类 | 64篇 |
预防医学 | 194篇 |
眼科学 | 28篇 |
药学 | 162篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 204篇 |
出版年
2022年 | 13篇 |
2021年 | 32篇 |
2020年 | 17篇 |
2019年 | 36篇 |
2018年 | 45篇 |
2017年 | 32篇 |
2016年 | 36篇 |
2015年 | 58篇 |
2014年 | 63篇 |
2013年 | 93篇 |
2012年 | 81篇 |
2011年 | 102篇 |
2010年 | 89篇 |
2009年 | 109篇 |
2008年 | 86篇 |
2007年 | 108篇 |
2006年 | 104篇 |
2005年 | 91篇 |
2004年 | 96篇 |
2003年 | 95篇 |
2002年 | 97篇 |
2001年 | 93篇 |
2000年 | 89篇 |
1999年 | 108篇 |
1998年 | 119篇 |
1997年 | 127篇 |
1996年 | 133篇 |
1995年 | 99篇 |
1994年 | 95篇 |
1993年 | 113篇 |
1992年 | 59篇 |
1991年 | 44篇 |
1990年 | 42篇 |
1989年 | 77篇 |
1988年 | 56篇 |
1987年 | 48篇 |
1986年 | 48篇 |
1985年 | 52篇 |
1984年 | 23篇 |
1983年 | 27篇 |
1982年 | 27篇 |
1981年 | 43篇 |
1980年 | 25篇 |
1979年 | 11篇 |
1978年 | 11篇 |
1977年 | 32篇 |
1976年 | 25篇 |
1975年 | 18篇 |
1974年 | 18篇 |
1967年 | 11篇 |
排序方式: 共有3257条查询结果,搜索用时 15 毫秒
91.
Remodeling of gap junctional coupling in hypertrophied right ventricles of rats with monocrotaline-induced pulmonary hypertension 总被引:7,自引:0,他引:7
Uzzaman M Honjo H Takagishi Y Emdad L Magee AI Severs NJ Kodama I 《Circulation research》2000,86(8):871-878
The present study investigates the remodeling of gap junctional organization in relation to changes in anisotropic conduction properties in hypertrophied right ventricles (RVs) of rats with monocrotaline (MCT)-induced pulmonary hypertension. In contrast to controls that showed immunolocalization of connexin43 (Cx43) labeling largely confined to the intercalated disks, RV myocytes from MCT-treated rats showed dispersion of Cx43 labeling over the entire cell surface. The disorganization of Cx43 labeling became more pronounced with the progression of hypertrophy. Desmoplakin remained localized to the intercalated disks, as in controls. In RV tissues, the proportion of Cx43 label at the intercalated disk progressively decreased. Quantitative analysis of en face views of intercalated disks revealed a significant decrease in the disk gap junctional density in RV tissues of MCT-treated rats (control, 0.18 versus MCT-treated, 0.14 at 2 weeks; control, 0.16 versus MCT-treated, 0.11 at 4 weeks). Conduction velocity in RVs parallel to the fiber orientation was significantly lower (30.2% [n=9]) in MCT-treated rats at 4 weeks than in control rats, whereas there was no significant difference observed in the conduction velocity across the fiber orientation between control and MCT-treated rats. The anisotropic ratio of MCT-treated rats (1.38+/-0.10) was significantly lower than that of control rats (1.98+/-0.12). These results suggest that RV hypertrophy induced by pressure overload is associated with both disorganization of gap junction distribution and alteration of anisotropic conduction properties. 相似文献
92.
Patient perspectives on de‐simplifying their single‐tablet co‐formulated antiretroviral therapy for societal cost savings
下载免费PDF全文
![点击此处可从《HIV medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Objectives
The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV‐infected patients are substantial, so cost‐saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de‐simplifying (i.e. switching) more expensive single‐tablet formulations (STFs) to less expensive generic‐based multi‐tablet components. We determined physician and patient perceptions and acceptance of STF de‐simplification within the context of a publicly funded ARV budget.Methods
Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de‐simplified to eligible generic co‐formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de‐simplification would be acceptable.Results
Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de‐simplifying could be safely achieved. Forty‐eight per cent of 221 patients surveyed were agreeable to de‐simplifying for altruistic reasons, 27% said no, and 25% said maybe.Conclusions
De‐simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de‐simplifying other STFs. Both physicians and patients agreed that selective de‐simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de‐simplification strategies seems warranted.93.
Dror Y; Gallagher R; Wara DW; Colombe BW; Merino A; Benkerrou M; Cowan MJ 《Blood》1993,81(8):2021-2030
We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor. 相似文献
94.
The toxic, bacterial metabolite sulfide is implicated in ulcerative colitis. Ulcerative colitis patients taking 5-aminosalicylic acid-containing drugs have lower fecal sulfide levels than those not taking these drugs. The effects of sulfasalazine, balsalazide, olsalazine, and 5-aminosalicylic acid on sulfide production were studied in a three-stage chemostat pulsed on days 1 to 3 with 5 g sulfasalazine (40 mM) and in pure cultures of amino acid-fermenting and sulfate-reducing bacteria. By the third day of sulfasalazine addition to the chemostat, sulfide concentrations in vessels 1 through 3 had dropped from 1.73, 1.78, and 1.43 mM to 0.01, 0.15, and 0.9 mM, respectively. In pure cultures, 50% inhibition of sulfide production from amino acids occurred at 2.5 +/- 0.05 mM for sulfasalazine, 5 +/- 0.2 mM for olsalazine, 6 +/- 1 mM for balsalazide, and more than 20 mM for 5-aminosalicylic acid. Fifty percent inhibition of sulfide production from sulfate occurred at 0.25 +/- 0.05 mM for sulfasalazine, 0.7 +/- 0.2 mM for balsalazide, and 9.0 +/- 1.0 mM for 5-aminosalicylic acid. The order of effectiveness of equimolar concentrations of drugs (most effective first) in this assay was sulfasalazine, then olsalazine (though given clinically at half the dose of other 5-aminosalicylic acid prodrugs) and balsalazide, and lastly 5-aminosalicylic acid. Inhibition of sulfide production by 5-aminosalicylic acid-containing drugs may contribute to their therapeutic effect in ulcerative colitis. 相似文献
95.
DeFelice ML Ruchelli ED Markowitz JE Strogatz M Reddy KP Kadivar K Mulberg AE Brown KA 《The American journal of gastroenterology》2003,98(8):1777-1782
OBJECTIVES: A relationship between autism and gastrointestinal (GI) immune dysregulation has been postulated based on incidence of GI complaints as well as macroscopically observed lymphonodular hyperplasia and microscopically determined enterocolitis in pediatric patients with autism. To evaluate GI immunity, we quantitatively assessed levels of proinflammatory cytokines, interleukin (IL)-6, IL-8, and IL-1beta, produced by intestinal biopsies of children with pervasive developmental disorders. METHODS: Fifteen patients, six with pervasive developmental disorders and nine age-matched controls, presenting for diagnostic colonoscopy were enrolled. Endoscopic biopsies were organ cultured, supernatants were harvested, and IL-6, IL-8, and IL-1beta levels were quantified by ELISA. Tissue histology was evaluated by blinded pathologists. RESULTS: Concentrations of IL-6 from intestinal organ culture supernatants of patients with pervasive developmental disorders (median 318.5 pg/ml, interquartile range 282.0-393.0 pg/ml) when compared with controls (median 436.9 pg/ml, interquartile range 312.6-602.5 pg/ml) were not significantly different (p = 0.0987). Concentrations of IL-8 (median 84,000 pg/ml, interquartile range 16,000-143,000 pg/ml) when compared with controls (median 177,000 pg/ml, interquartile range 114,000-244,000 pg/ml) were not significantly different (p = 0.0707). Concentrations of IL-1beta (median 0.0 pg/ml, interquartile range 0.0-94.7 pg/ml) when compared with controls (median 0.0 pg/ml, interquartile range 0.0-60.2 pg/ml) were not significantly different (p = 0.8826). Tissue histology was nonpathological for all patients. CONCLUSIONS: We have demonstrated no significant difference in production of IL-6, IL-8, and IL-1beta between patients with pervasive developmental disorders and age-matched controls. In general, intestinal levels of IL-6 and IL-8 were lower in patients with pervasive developmental disorders than in age-matched controls. These data fail to support an association between autism and GI inflammation. 相似文献
96.
Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane. 相似文献
97.
Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V 总被引:6,自引:1,他引:6
Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC. 相似文献
98.
99.