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131.
Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs) is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC) or 6 days (E6d HPC). Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO) was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF) regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC). Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1). An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection. 相似文献
132.
Yalai Bai Huan Cheng Jennifer Bordeaux Veronique Neumeister Sudha Kumar David L. Rimm David F. Stern 《PloS one》2013,8(11)
Background
HER2/Neu (ErbB-2) overexpression, which occurs in 15–20% of breast cancer cases, is associated with better response to treatment with the drug trastuzumab. PhosphoHER2 (pHER2) has been evaluated for prediction of response to trastuzumab. Both markers are heterogeneously detected and are potentially subject to loss as a consequence of delayed time to fixation. Here, we quantitatively assess both markers in core needle biopsies (CNBs) and matched tumor resections to assess concordance between the core and the resection and between HER2 and pHER2.Methods
A selected retrospective collection of archival breast cancer cases yielded 67 cases with both core and resection specimens. Both HER2 and pTyr1248HER2 were analyzed by the AQUA® method of quantitative immunofluorescence on each specimen pair.Results
Both HER2 immunoreactivity (P<0.0001) and pTyr1248HER2 immunoreactivity (P<0.0001) were lower in resections relative to CNB specimens. However, clinical implications of this change may not be evident since no case changed from 3+ (CNB) to negative (resection). Assessment of pTyr1248HER2 showed no direct correlation with HER2 in either CNB or resection specimens.Conclusions
The data suggest that measurement of both HER2 and phospho- Tyr1248HER2, in formalin-fixed tissue by immunological methods is significantly affected by pre-analytic variables. The current study warrants the adequate handling of resected specimens for the reproducible evaluation of HER2 and pHER2. The level of pTyr1248HER2, was not correlated to total HER2 protein. Further studies are required to determine the significance of these observations with respect to response to HER2 directed therapies. 相似文献133.
134.
Li Gao Hao Guo Nan Ye Yudi Bai Xin Liu Ping Yu Yang Xue Shufang Ma Kewen Wei Yan Jin Lingying Wen Kun Xuan 《PloS one》2013,8(6)
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder of the peripheral nervous system resulting from mutations in neurotrophic tyrosine kinase receptor 1 gene (NTRK1), which encodes the high-affinity nerve growth factor receptor TRKA. Here, we investigated the oral and craniofacial manifestations of a Chinese patient affected by autosomal-recessive CIPA and identified compound heterozygosity in the NTRK1 gene. The affected boy has multisystemic disorder with lack of reaction to pain stimuli accompanied by self-mutilation behavior, the inability to sweat leading to defective thermoregulation, and mental retardation. Oral and craniofacial manifestations included a large number of missing teeth, nasal malformation, submucous cleft palate, severe soft tissue injuries, dental caries and malocclusion. Histopathological evaluation of the skin sample revealed severe peripheral nerve fiber loss as well as mild loss and absent innervation of sweat glands. Ultrastructural and morphometric studies of a shed tooth revealed dental abnormalities, including hypomineralization, dentin hypoplasia, cementogenesis defects and a dysplastic periodontal ligament. Genetic analysis revealed a compound heterozygosity- c.1561T>C and c.2057G>A in the NTRK1 gene. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with CIPA and provides additional insight for clinical and molecular diagnosis. 相似文献
135.
Yanxin Gong Yuanqing Wang Yang Wang Fangyuan Mao Bin Bai Haibing Wang Qian Li Xun Jin Xu Wang Jin Meng 《Palaeontology》2020,63(4):547-564
Lophialetidae is an extinct group of endemic Asiatic tapiroids that are widely distributed in the Eocene sediments of Asia. Schlosseria magister and Lophialetes expeditus are the most abundant species in this family. However, their dietary and ecological characteristics are largely unknown. For the first time, we reconstruct the palaeodiet and habitat of these two lophialetids using a combination of mesowear and stable carbon isotope analysis of fossil teeth excavated from the Erlian Basin, China. Mesowear analysis (n = 141) suggests that the dietary structure of S. magister and L. expeditus shifted from less to more abrasive diets from ~52 to ~42 Ma. Stable carbon isotope analysis (n = 137) suggests that the habitats of S. magister and L. expeditus became drier and/or more open through time. The dietary shifts of the two lophialetids are consistent with evident changes in habitat. The changes in the diet and habitat were probably related to global climate change during that time period. The gradual drop in global temperatures during the early–middle Eocene led to a drier and more open terrestrial ecosystem in the Erlian Basin, probably resulting in changes in floral composition of the environment inhabited by S. magister and L. expeditus. Hence, herbivores highly susceptible to vegetation modification had to develop new resource exploitation strategies to adapt to these changes. Schlosseria magister, considered to be the sister-group of L. expeditus and with a low level of ecological flexibility, was unable to adapt to the habitat changes finally becoming extinct at ~45 Ma. 相似文献
136.
Hong Sung Hyun Singh Sudhir Tripathi Bhumi Nath Mondal Suvendu Lee Sangmin Jung Hyun Suk Cho Chuloh Kaur Shubhpreet Kim Jin-Hong Lee Sungbeom Bai Hyoung-Woo Bae Hyeun-Jong Lee Sang Yeol Lee Seung Sik Chung Byung Yeoup 《Protoplasma》2020,257(3):807-817
Protoplasma - Alkyl hydroperoxide reductase subunit F (AhpF) is a well-known flavoprotein that transfers electrons from pyridine nucleotides to the peroxidase protein AhpC via redox-active... 相似文献
137.
Kong Tao Zhang Shu-Hui Zhang Cai Zhang Ji-Liang Yang Fan Wang Guo-Yong Yang Zi-Jun Bai Dong-Ying Shi Yun-Yun Liu Tian-Qi Li Hai-Long 《Biological trace element research》2020,194(2):443-443
Biological Trace Element Research - The original version of this article unfortunately contained a mistake. The correct title should be “The Effects of 50 nm Unmodified Nano-ZnO on Lipid... 相似文献
138.
Xiao Xiao Bai Peng Cao Shuqiang Jiang Youjing Liang Weibo Wang Tao Luo Xiaolei Guan Qiaozhi Gao Linbo Zhang Lin 《Neurochemical research》2020,45(4):928-939
Neurochemical Research - High-throughput and bioinformatics technology have been broadly applied to demonstrate the key molecules involved in traumatic brain injury (TBI), while no study has... 相似文献
139.
Zhenpeng Li Zeqiong Cai Weixin Fu Ying Liu Chenglei Tian He Wang Tongtong Fu Zhenzhou Wu Donghai Wu Yongxin Jin Zhihui Cheng Naohiro Terada Lin Liu Weihui Wu Shouguang Jin Fang Bai 《Biotechnology and bioengineering》2020,117(3):816-831
Intracellular delivery of functional proteins is of great interest for basic biological research as well as for clinical applications. Transfection is the most commonly used method, however, it is not applicable to large-scale manipulation and inefficient in important cell types implicated in biomedical applications, such as epithelial, immune and pluripotent stem cells. In this study, we explored a bacterial type III secretion system (Bac-T3SS)-mediated proteofection method to overcome these limitations. An attenuated Pseudomonas aeruginosa vector was constructed, which has features of low toxicity, high T3SS activity, and self-limiting growth. Compared to the method of transfection, the Bac-T3SS showed significantly higher efficiencies of Cre recombinase translocation and target site recombination for hard-to-transfect human cell lines. Furthermore, through the delivery of β-lactamase in live animals, we demonstrated the feasibility and biosafety of in vivo application of the Bac-T3SS. This study provided an efficient and low-cost proteofection strategy for laboratory use as well as for application in large-scale cell manipulations. 相似文献
140.