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31.
Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery 总被引:11,自引:3,他引:11
Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV. 相似文献
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The aim of this case report was to present a case of multiple calcified tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in an endodontic clinic. A detailed discussion on the differential diagnosis of similar such calcification found in the same region is also presented. A 14‐year‐old girl was referred to our department with the complaint of painless swelling in the left side of the lower jaw. Clinical and radiographical examinations were performed, leading to the initial diagnosis of chronic periapical abscess. The patient's medical history was re‐evaluated. Advanced imaging and excisional biopsy were performed in order to confirm the final diagnosis. Regarding the presenting signs and symptoms of bilateral carious mandibular molars, a periapical inflammatory process was considered in the provisional diagnosis. A thorough examination and investigations were suggestive of cervical tuberculous lymphadenitis (scrofula), and the patient underwent excision of the same. The clinician should consider the possibility of chronic granulomatous inflammatory lesions in the differential diagnosis of radiopaque lesions. 相似文献
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异基因造血干细胞移植(allo-HSCT)是许多血液系统恶性肿瘤和严重免疫缺陷的一种治疗方法,而慢性移植物抗宿主病(cGVHD)是移植后主要并发症之一,严重影响了患者的生活质量。cGVHD可攻击眼部的所有靶组织,比较多见的是泪腺、眼睑、结膜、角膜、角膜缘和睑板腺等,其病理生理过程为炎症反应和纤维化。尽管现在许多国内外的研究者逐步开始了对该病深入的探索并获得了很多的新发现,但其病理、发病机制仍未完全清楚,并且目前无统一、有效的治疗方法。临床上对于该病的治疗通常是在已出现症状的时候,此时靶组织很可能发生了不可逆、永久性的损害,从而造成迁延难治的局面。因此文章主要对近年来眼部cGVHD的病理及发病机制的研究进展进行阐述,以期对该病的治疗方案提供新的指导。 相似文献
37.
Rebecca Dann Tarik Hadi Emilie Montenont Ludovic Boytard Dornaszadat Alebrahim Jordyn Feinstein Nicole Allen Russell Simon Krista Barone Kunihiro Uryu Yu Guo Caron Rockman Bhama Ramkhelawon Jeffrey S. Berger 《Journal of the American College of Cardiology》2018,71(1):53-65
Background
Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear.Objectives
The authors sought to investigate the role of platelets in a cohort of symptomatic PAD.Methods
The authors profiled platelet activity, mRNA, and effector roles in patients with symptomatic PAD and in healthy controls. Patients with PAD and carotid artery stenosis were recruited into ongoing studies (NCT02106429 and NCT01897103) investigating platelet activity, platelet RNA, and cardiovascular disease.Results
Platelet RNA sequence profiling mapped a robust up-regulation of myeloid-related protein (MRP)-14 mRNA, a potent calcium binding protein heterodimer, in PAD. Circulating activated platelets were enriched with MRP-14 protein, which augmented the expression of the adhesion mediator, P-selectin, thereby promoting monocyte–platelet aggregates. Electron microscopy confirmed the firm interaction of platelets with monocytes in vitro and colocalization of macrophages with MRP-14 confirmed their cross talk in atherosclerotic manifestations of PAD in vivo. Platelet-derived MRP-14 was channeled to monocytes, thereby fueling their expression of key PAD lesional hallmarks and increasing their directed locomotion, which were both suppressed in the presence of antibody-mediated blockade. Circulating MRP-14 was heightened in the setting of PAD, significantly correlated with PAD severity, and was associated with incident limb events.Conclusions
The authors identified a heightened platelet activity profile and unraveled a novel immunomodulatory effector role of platelet-derived MRP-14 in reprograming monocyte activation in symptomatic PAD. (Platelet Activity in Vascular Surgery and Cardiovascular Events [PACE]; NCT02106429; and Platelet Activity in Vascular Surgery for Thrombosis and Bleeding [PIVOTAL]; NCT01897103) 相似文献38.
Elizabeth LM Barr Stephen R Lord Hylton B Menz Hal Kendig 《Disability and rehabilitation》2013,35(16):917-923
Purpose.?To determine whether foot and leg problems are independently associated with functional status in a community sample of older people after adjusting for the influence of socio-demographic, physical and medical factors.Method.?Data were analysed from the Health Status of Older People project, a population-based study involving a random sample of 1000 community-dwelling people aged 65?–?94 years (533 females, 467 males, mean age 73.4 years?±?5.87). A structured interview and brief physical examination were used to investigate the associations between self-reported foot and leg problems and functional status. Functional status was assessed using: (i) timed ‘Up & Go’ test, (ii) self-reported difficulty climbing stairs, (iii) self-reported difficulty walking one kilometer, (iv) self-reported difficulty performing instrumental activities of daily living (IADLs), and (v) self-reported history of one or more falls in the previous 12 months. These associations were then explored after adjusting for socio-demographic, physical and medical factors.Results.?Thirty-six percent of the sample reported having foot or leg problems. Univariate analyses revealed that people with foot and leg problems were significantly more likely to exhibit poorer functional status in all parameters measured. After adjusting for socio-demographic, physical and medical factors, foot and leg problems remained significantly associated with impaired timed ‘Up & Go’ performance (OR?=?2.15, 95%CI 1.55?–?2.97), difficulty climbing stairs (OR?=?3.33, 95%CI 1.98?–?5.61), difficulty walking one kilometer (OR?=?3.13, 95%CI 2.09?–?4.69), and history of falling (OR?=?1.73, 95%CI 1.26?–?2.37).Conclusions.?Foot and leg problems are reported by one in three community-dwelling people aged 65 years and older. Independent of the influence of age, gender, common medical conditions and other socio-demographic factors, foot and leg problems have a significant impact on the ability to perform functional tasks integral to independent living. 相似文献
39.
T. Ho¨kfelt L. Skirboll J.F. Rehfeld M. Goldstein K. Markey O. Dann 《Neuroscience》1980,5(12):2093-2124
Using indirect immunofluorescence histochemistry combined with the elution and restaining technique ofTramu, Pillez &Leonardelli (1978), evidence has been obtained that at least some mesencephalic dopamine neurons contain a cholecystokinin (CCK)-like peptide, mainly the C-terminal octapeptide (CCK-8). These cholecystokinin-dopamine cells were present predominantly in the ventral tegmental area (A10), but were also found in the pars lateralis of the substantia nigra and, mainly at a rostral level, in the zona compacta. Terminal nerve fibre networks containing a cholecystokinin-like peptide and tyrosine hydroxylase (the marker for dopamine neurons), respectively, were found on adjacent sections with overlapping distribution patterns in the caudal-medial parts of the nucleus accumbens, the medial tuberculum olfactorium, the bed nucleus of the stria terminalis, the caudal periventricular caudate nucleus and the central amygdaloid nucleus. After injection of 6-hydroxy-dopamine into the lateral hypothalamus or into the ventral mesencephalon, or a frontal hemisection at the hypothalamic level, a marked reduction of both types of fibres was observed in these areas. By combining the indirect immunofluorescence technique with the retrograde tracing of fluorescent dyes, it could be established that cholecystokinin-dopamine cell bodies in the ventral tegmental area project to the caudal, medial nucleus accumbens. Colchicine injected into the lateral hypothalamus caused overlapping accumulations of cholecystokinin- and tyrosine hydroxylase-like immunoreactivity caudal to the injection site. Similar findings were seen caudal to a frontal hypothalamic hemitransection.Cholecystokinin immunoreactive neuronal structures were observed in many other brain areas and some systems of interest in relation to the ascending mesencephalic dopamine neurons are described, such as cholecystokinin fibres present in the dorsal aspects of the zona compacta and in patches in the caudate nucleus. No evidence was obtained that these two latter and some other cholecystokinin immunoreactive nerve terminal systems contained dopamine.The findings demonstrate the coexistence of a cholecystokinin-like peptide and dopamine in a population of mesencephalic neurons projecting to limbic areas. 相似文献
40.
The role of fungal spores in thunderstorm asthma 总被引:2,自引:0,他引:2
STUDY OBJECTIVES: To document the existence and investigate the etiology of "thunderstorm asthma," which has been reported sporadically over the past 20 years. DESIGN: We assessed the relationship between thunderstorms, air pollutants, aeroallergens, and asthma admissions to a children's hospital emergency department over a 6-year period. RESULTS: During thunderstorm days (n = 151 days) compared to days without thunderstorms (n = 919 days), daily asthma visits increased from 8.6 to 10 (p < 0.05), and air concentrations of fungal spores doubled (from 1,512 to 2,749/m(3)), with relatively smaller changes in pollens and air pollutants. Daily time-series analyses across the 6 years of observation, irrespective of the presence or absence of thunderstorms, demonstrated that an increase in total spores, equivalent to its seasonal mean, was associated with a 2.2% (0.9% SE) increase in asthma visits. CONCLUSIONS: Our results support a relationship between thunderstorms and asthma, and suggest that the mechanism may be through increases in spores that exacerbate asthma. Replication in other climates is suggested to determine whether these findings can be generalized to other aeroallergen mixes. 相似文献