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71.
Plemper RK Erlandson KJ Lakdawala AS Sun A Prussia A Boonsombat J Aki-Sener E Yalcin I Yildiz I Temiz-Arpaci O Tekiner B Liotta DC Snyder JP Compans RW 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(15):5628-5633
Measles virus (MV) constitutes a principal cause of worldwide mortality, accounting for almost 1 million deaths annually. Although a live-attenuated vaccine protects against MV, vaccination efficiency of young infants is low because of interference by maternal antibodies. Parental concerns about vaccination safety further contribute to waning herd immunity in developed countries, resulting in recent MV outbreaks. The development of novel antivirals that close the vaccination gap in infants and silence viral outbreaks is thus highly desirable. We previously identified a microdomain in the MV fusion protein (F protein) that is structurally conserved in the paramyxovirus family and constitutes a promising target site for rationally designed antivirals. Here we report the template-based development of a small-molecule MV inhibitor, providing proof-of-concept for our approach. This lead compound specifically inhibits fusion and spread of live MV and MV glycoprotein-induced membrane fusion. The inhibitor induces negligible cytotoxicity and does not interfere with receptor binding or F protein biosynthesis or transport but prevents F protein-induced lipid mixing. Mutations in the postulated target site alter viral sensitivity to inhibition. In silico docking of the compound in this microdomain suggests a binding model that is experimentally corroborated by a structure-activity analysis of the compound and the inhibition profile of mutated F proteins. A second-generation compound designed on the basis of the interaction model shows a 200-fold increase in antiviral activity, creating the basis for novel MV therapeutics. This template-based design approach for MV may be applicable to other clinically relevant members of the paramyxovirus family. 相似文献
72.
The lung is one of the most sensitive organs to ionizing radiation, and damage to normal lung tissue remains a major dose limiting factor for patients receiving radiation to the thorax. Radiation induced lung injury (RILI) which is also named as “radiation pneumonpathy” is a continuous process and regarded as the result of an abnormal healing response. It has been shown that transforming growth factor β-1 (TGF-β1) plays an integral role in the radiation induced lung fibrosis formation by promoting the chemoattraction of fibroblasts and their conversion to myofibroblasts. Halofuginone is a, low molecular weight plant derived alkaloid, isolated from the Dichroa febrifuga plant that exhibits antifibrotic activity and inhibition of type I collagen synthesis. Halofuginone has been shown to protect against radiation induced soft tissue fibrosis by virtue of inhibiting various members of TFG-β signaling pathway. By the light of these findings, we hypothesize that Halofuginone may be able to ameliorate the radiation induced lung fibrosis. 相似文献
73.
Risk of vasovagal syncope and cardiac arrhythmias in children with mitral valve prolapse 总被引:1,自引:0,他引:1
OBJECTIVE: Postural phenomena, cardiac arrhythmias and autonomic dysfunction are responsible for presyncope and syncope in patients with mitral valve prolapse (MVP). In this study, arrhythmia and vasovagal syncope incidence were investigated in children with MVP. METHODS: Between April 2005 and December 2006, 37 children with MVP and 26 healthy children were evaluated.Telecardiography, electrocardiography (ECG), echocardiography, Holter monitoring, exercise test and head-up tilt test were performed. RESULTS: The MVP group consisted of 19 boys and 18 girls with a mean age of 11.8 years. The control group was similar with respect to age and gender. Telecardiography, ECG, Holter monitoring, exercise test and QTc of all children were within normal limits.There was a statistically significant difference between the two groups in terms of QT dispersion. The tilt table test was positive in 11 of 37 (29.7%) children with MVP and in 1 of 26 (3.8%) normal healthy children. This difference was statistically significant (P < 0.01). CONCLUSION: Arrhythmia and syncope frequency was found to be higher in children with MVP than in the normal population. The risk of vasovagal syncope indicated by a positive tilt test was found to be increased in children with MVP. Therefore, patients and families must be informed about the conditions that may predispose to vasovagal syncope and caution should be recommended in these patients. 相似文献
74.
Faruk Incecik Mehmet N. Ozbek Serdal Gungor Stefano Pepe Ozlem M. Herguner Neslihan Onenli Mungan Sabiha Gungor Sakir Altunbasak 《Annals of Indian Academy of Neurology》2013,16(4):720-722
Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.Key Words: Child, multiple sulfatase deficiency, sulfatase-modifying factor 1 gene 相似文献
75.
Miral S Gencer O Inal-Emiroglu FN Baykara B Baykara A Dirik E 《European child & adolescent psychiatry》2008,17(1):1-8
Objective The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of
Autistic Disorder (AD).
Method This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of
8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators
and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory
tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day.
Results The reduction from baseline in Ritvo–Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale
V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist
(ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further
increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS
sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05).
Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language
skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated
in the treatment of AD. 相似文献
76.
Hilal Akalin Izem Olcay Sahin Seyma Aktas Paskal Busra Tan Ezgi Yalcinkaya Mikail Demir Mustafa Yakubi Busra Ozguc Caliskan Ozlem Gokce Ekinci Mehmet Ercan Tugce Yasar Kucuk Gizem Gokgoz Aslihan Kiraz Huseyin Per Mahmut Tuncay Ozgun Numan Baydilli Yusuf Ozkul Munis Dundar 《Journal of clinical laboratory analysis》2024,38(1-2):e24997
77.
Fetal nasal bone hypoplasia in the second trimester: Comparison of diagnostic methods for predicting trisomy 21 (Down syndrome) 下载免费PDF全文
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