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Ahmed H. Ibrahim Hatem R. Ismael Ahmed M. Samy 《Pharmaceutical development and technology》2018,23(4):358-369
AbstractThe objective of this study was to enhance physiochemical properties as well as oral bioavailability of the poorly water soluble drug fenofibrate (FB), through preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic carriers. Formulations were optimized by 32 full factorial design (FFD) with PVP-K30 level (X1) and poloxamer 188 level (X2) as independent variables and particle size (Y1), zeta potential (Y2), drug content (Y3) and dissolution rate (T90, [Y4]) as dependent variables. Optimized FB nanoparticles were physicochemically evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic, pharmacodynamics and histological finding of optimized formulation were performed on rabbits. Y1 and Y4 were significantly affected by independent variables while Y2 and Y3 were not affected. Physicochemical characterization showed the drug was in amorphous state, nanometer range and pharmacophore of FB was preserved. Administration of optimized FB tablets to rabbits with fatty liver led to significant reduction (p?<?0.001) in serum lipids. Moreover, histological analysis of liver specimens confirmed the improved efficacy in animals with fatty liver. In this study, we confirmed that ASDs of FB had beneficial effects on managing fatty liver and serum lipids level in hyperlipidemic rabbits. 相似文献
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Rashad Al-Salahi Moustapha E. Moustapha Hatem A. Abuelizz Abdulrahman I. Alharthi Khalid A. Alburikan Ismail T. Ibrahim Mohamed Marzouk Mohamed A. Motaleb 《Saudi Pharmaceutical Journal》2018,26(8):1120-1126
3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2?±?1.22% and the in vitro studies showed that the target compound was stable for up to 24?h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells. 相似文献
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Atteeq U. Rehman Maryam Najafi Marios Kambouris Lihadh Al‐Gazali Periklis Makrythanasis Abolfazl Rad Reza Maroofian Anna Rajab Zornitza Stark Jill V. Hunter Zeineb Bakey Mari J. Tokita Weimin He Francesco Vetrini Andrea Petersen Federico A. Santoni Hanan Hamamy Kaman Wu Fatma Al‐Jasmi Martin Helmstdter Sebastian J. Arnold Fan Xia Christopher Richmond Pengfei Liu Ehsan Ghayoor Karimiani GholamReza Karami Madani Sebastian Lunke Hatem El‐Shanti Christine M. Eng Stylianos E. Antonarakis Jozef Hertecant Magdalena Walkiewicz Yaping Yang Miriam Schmidts 《Human mutation》2019,40(3):267-280
Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway. 相似文献
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Hatem G. Said AbdulRahman A. Babaqi Aly Mohamadean Ahmed H. Khater Mohamed H. Sobhy 《International orthopaedics》2014,38(5):1063-1066
Purpose
The proximal part of the long head of the biceps muscle has become a recognized cause of significant shoulder pain. Tenodesis of the long head of the biceps has been advocated as a treatment for pain resulting from biceps tendonopathy, biceps instability, and biceps tendon tears. All of these pathologies may be encountered during rotator cuff, SLAP or Bankart surgery, or in isolation. Several techniques have been described for this tenodesis, including various arthroscopic and subpectoral methods.Methods
We present a modified bone bridge technique of Mazzocca et al., for subpectoral biceps tenodesis. In this technique we tenodese the tendon through two bone tunnels back over the muscle itself without implants.Results
Application of this technique on 30 patients (ages 25–48 years) with short-term follow-up of 12–18 months showed statistically significant improvement (P value < 0.05) of the mean Constant and Oxford shoulder scores (pre-operative mean scores were 39.03 and 21.3, respectively, while postoperative mean scores were 76.43 and 44.8, respectively).Conclusion
This technique has potential advantages as it allows the possibility of adjusting the tension of the biceps tendon before final suturing, in addition to quicker soft tissue healing. 相似文献8.
Dura to spinal cord distance at different vertebral levels in children and its implications on epidural analgesia: A retrospective MRI‐based study 下载免费PDF全文
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Yasser Salama Saleh Albanyan Marta Szybowska Garrett Bullivant Bailey Gallinger Rachel H. Giles Sylvia Asa Chansonette Badduke Andreea Chiorean Harriet Druker Shereen Ezzat Fady Hannah-Shmouni Karen G. Hernandez Cara Inglese Payal Jani Yuvreet Kaur Hatem Krema Lior Krimus Normand Laperriere Zsuzanna Lichner Ozgur Mete Marisa Sit Gelareh Zadeh Michael A.S. Jewett David Malkin Tracy Stockley Jonathan D. Wasserman Wei Xu Nathan F. Schachter Raymond H. Kim 《Clinical genetics》2019,96(5):461-467
Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or β-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL. 相似文献
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