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31.
A Robust Approach for Blind Detection of Balanced Chromosomal Rearrangements with Whole‐Genome Low‐Coverage Sequencing 下载免费PDF全文
Hua Hu Xiuhua Wang Haixiao Chen Kwong Wai Choy Huamei Hu Yanling Dong Bin Hu Juchun Xu Yang Long Sujie Cao Hui Chen Wen‐Jing Wang Hui Jiang Fengping Xu Hong Yao Xun Xu Zhiqing Liang 《Human mutation》2014,35(5):625-636
Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next‐generation sequencing has been reported to detect BCA‐associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application. Here, we provide a whole‐genome low‐coverage sequencing approach to detect BCA events independent of knowing the affected regions and with low false positives. First, six samples containing BCAs were used to establish a detection protocol and assess the efficacy of different library construction approaches. By clustering anomalous read pairs and filtering out the false‐positive results with a control cohort and the concomitant mapping information, we could directly detect BCA events for each sample. Through optimizing the read depth, BCAs in all samples could be blindly detected with only 120 million read pairs per sample for data from a small‐insert library and 30 million per sample for data from nonsize‐selected mate‐pair library. This approach was further validated using another 13 samples that contained BCAs. Our approach advances the application of high‐throughput whole‐genome low‐coverage analysis for robust BCA detection—especially for clinical samples—without the need for karyotyping. 相似文献
32.
Thomas Haselhorst Ka Tim Choy Hui‐Ling Yen Joseph S. M. Peiris Mark von Itzstein John M. Nicholls 《Influenza and other respiratory viruses》2014,8(2):235-242
Objectives
The main function of influenza neuraminidase (NA) involves enzymatic cleavage of sialic acid from the surface of host cells resulting in the release of the newly produced virions from infected cells, as well as aiding the movement of virions through sialylated mucus present in the respiratory tract. However, there has previously been little information on the binding affinity of different forms of sialylated glycan with NA. Our objectives were then to investigate both sialic acid binding and cleavage of neuraminidase at an atomic resolution level.Design
Nuclear magnetic resonance (NMR) spectroscopy was used to investigate pH and temperature effects on binding and cleavage as well as to interrogate the selectivity of human-like or avian-like receptors for influenza neuraminidase N1 derived from a range of different influenza virus strains including human seasonal H1N1, H1N1pdm09 and avian H5N1.Results
We demonstrated that an acidic pH and physiological temperature are required for efficient NA enzymatic activity; however a change in the pH had a minimum effect on the NA-sialic acid binding affinity. Our data comparing α-2,3- and α-2,6-sialyllactose indicated that the variation in neuraminidase activity on different ligands correlated with a change in binding affinity. Epitope mapping of the sialylglycans interacting with NAs from different viral origin showed different binding profiles suggesting that different binding conformations were adopted.Conclusions
The data presented in this study demonstrated that physicochemical conditions (pH in particular) could affect the NA enzymatic activity with minor effect on ligand binding. NA cleavage specificity seemed to be associated with a difference in binding affinity to different ligands, suggesting a relationship between the two events. These findings have implications regarding the replication cycle of influenza infection in the host where different sialidase activities would influence penetration through the respiratory mucin barrier and the release of the newly generated virus from the infected cells. 相似文献33.
Ji Eun Lee Subin Park Min Park Myung Hun Kim Chun Gwon Park Seung Ho Lee Sung Yoon Choi Byung Hwi Kim Hyo Jin Park Ji-Ho Park Chan Yeong Heo Young Bin Choy 《Acta biomaterialia》2013,9(9):8318-8327
Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical strength of the suture itself – strength that is essential for successful wound closure. Thus, it is not easy to control drug delivery with sutures, and the drug-delivery surgical sutures available for clinical use are now limited to anti-infection roles. Here, we demonstrate a surgical suture enabled to provide controlled delivery of a pain-relief drug and, more importantly, we demonstrate how it can be fabricated to maintain the mechanical strength of the suture itself. For this purpose, we separately prepare a drug-delivery sheet composed of a biocompatible polymer and a pain-relief drug, which is then physically assembled with a type of surgical suture that is already in clinical use. In this way, the drug release profiles can be tailored for the period of therapeutic need by modifying only the drug-loaded polymer sheet without adversely influencing the mechanical strength of the suture. The drug-delivery sutures in this work can effectively relieve the pain at the surgical site in a sustained manner during the period of wound healing, while showing biocompatibility and mechanical properties comparable to those of the original surgical suture in clinical use. 相似文献
34.
Hexagonal and wormhole-type mesoporous geopolymers were developed by controlling the concentration of a structure directing agent (cetrimonium bromide, CTAB) with fixed ratios of Si/Al, KOH/(Si + Al), and H2O/(Si + Al), and their detailed porous structures were confirmed by TEM, N2 adsorption–desorption and X-ray diffraction measurements. The as-prepared geopolymers were then used as templates to replicate porous carbons with various structures and porosities for CO2 adsorption. To understand the correlation between the CO2 adsorptivity and porous structures, we tuned the porosity of the geopolymer-templated carbons by modifying the structures of the geopolymers. The porous carbons obtained from the hexagonal-type porous geopolymers were found to be composed of the aggregates of carbon nanowires exhibiting large particles, while those obtained from the wormhole-like porous geopolymers were determined to be wormhole type as well, as evidenced by TEM and X-ray diffraction studies. According to the CO2 adsorption isotherms of the porous carbons, the aggregates of carbon nanowires exhibited the highest CO2 adsorptivity due to their highest microporosity and largest specific surface area.We report the synthesis of microporous carbon through a geopolymer route starting from natural clay kaolinite. 相似文献
35.
Godwin G.H. Choy John A. Roe Sarah L. Whitehouse Kara S. Cashman Ross W. Crawford 《The Journal of arthroplasty》2013
The standard Exeter stem has a length of 150 mm with offsets 37.5 to 56 mm. Shorter stems of lengths 95, 115 and 125 mm with offsets 35.5 mm or less are available for patients with smaller femurs. Concern has been raised regarding the behavior of the smaller implants. This paper analyzed data from the Australian Orthopaedic Association National Joint Replacement Registry comparing survivorship of stems of offset 35.5 mm or less with the standard stems of 37.5 mm offset or greater. At 7 years, there was no significant difference in the cumulative percent revision rate in the short stems (3.4%, 95% CI 2.4-4.8%) compared with the standard length stems (3.5%, 95% CI 3.3-3.8%) despite its use in a greater proportion of potentially more difficult developmental dysplasia of the hip cases. 相似文献
36.
37.
Sang Ki Lee Ju Sang Park Won Sik Choy 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2013,23(6):705-713
Intramedullary screw fixation is the most common treatment for fifth metatarsal base fractures. Screw application does not achieve accurate reduction in fracture with small fragments, osteoporotic bone, or Lawrence zone 1 fractures, however. On the basis of similar anatomical architectures between the distal ulna and the fifth metatarsal base, the purpose of this study was to assess the results of a locking compression plate (LCP) distal ulna hook plate in stabilizing displaced zone 1 or 2 fifth metatarsal base fractures. Nineteen patients with Lawrence zone 1 (n = 12) or 2 (n = 7) fractures of the fifth metatarsal base were treated surgically with an LCP distal ulna hook plate. The patients were evaluated clinically and radiographically, and functional outcomes were graded by using the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scoring system. Radiographic bony union was obtained in all patients, at an average of 7.4 weeks. The mean AOFAS midfoot score improved from 26 (range, 0–45) preoperatively to 94 (range, 72–100) points at the final follow-up. There were three patients with post-traumatic cubometatarsal arthrosis and one patient with sural nerve neuropraxia. In our experience, the distal ulna hook plate achieves a high rate of bony consolidation and anatomically suitable fixation in zone 1 or 2 fifth metatarsal base fractures. We also suggest that the LCP distal ulna hook plate should be considered as an alternative treatment in multifragmentary, osteoporotic, and tuberosity avulsion (zone 1) fifth metatarsal base fractures. 相似文献
38.
39.
Park SJ Kim GY Choy HE Hong YJ Saif LJ Jeong JH Park SI Kim HH Kim SK Shin SS Kang MI Cho KO 《Archives of virology》2007,152(10):1885-1900
Summary Although winter dysentery (WD), which is caused by the bovine coronavirus (BCoV) is characterized by the sudden onset of diarrhea
in many adult cattle in a herd, the pathogenesis of the WD-BCoV is not completely understood. In this study, colostrum-deprived
calves were experimentally infected with a Korean WD-BCoV strain and examined for viremia, enteric and nasal virus shedding
as well as for viral antigen expression and virus-associated lesions in the small and large intestines and the upper and lower
respiratory tract from 1 to 8 days after an oral infection. The WD-BCoV-inoculated calves showed gradual villous atrophy in
the small intestine and a gradual increase in the crypt depth of the large intestine. The WD-BCoV-infected animals showed
epithelial damage in nasal turbinates, trachea and lungs, and interstitial pneumonia. The WD-BCoV antigen was detected in
the epithelium of the small and large intestines, nasal turbinates, trachea and lungs. WD-BCoV RNA was detected in the serum
from post-inoculation day 3. These results show that the WD-BCoV has dual tropism and induces pathological changes in both
the digestive and respiratory tracts of calves. To our knowledge, this is the first detailed report of dual enteric and respiratory
tropisms of WD-BCoV in calves. Comprehensive studies of the dual tissue pathogenesis of the BCoV might contribute to an increased
understanding of similar pneumoenteric CoV infections in humans. 相似文献
40.