全文获取类型
收费全文 | 970篇 |
免费 | 155篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 10篇 |
妇产科学 | 1篇 |
基础医学 | 155篇 |
口腔科学 | 10篇 |
临床医学 | 20篇 |
内科学 | 68篇 |
皮肤病学 | 12篇 |
神经病学 | 112篇 |
特种医学 | 5篇 |
外科学 | 48篇 |
综合类 | 176篇 |
预防医学 | 28篇 |
眼科学 | 7篇 |
药学 | 66篇 |
中国医学 | 425篇 |
肿瘤学 | 19篇 |
出版年
2024年 | 24篇 |
2023年 | 75篇 |
2022年 | 93篇 |
2021年 | 100篇 |
2020年 | 85篇 |
2019年 | 65篇 |
2018年 | 36篇 |
2017年 | 39篇 |
2016年 | 30篇 |
2015年 | 31篇 |
2014年 | 68篇 |
2013年 | 42篇 |
2012年 | 51篇 |
2011年 | 63篇 |
2010年 | 32篇 |
2009年 | 30篇 |
2008年 | 27篇 |
2007年 | 20篇 |
2006年 | 29篇 |
2005年 | 24篇 |
2004年 | 21篇 |
2003年 | 19篇 |
2002年 | 16篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 12篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 16篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有1168条查询结果,搜索用时 343 毫秒
61.
Damián Pérez-Mazliah Francis M. Ndungu Racheal Aye Jean Langhorne 《Immunological reviews》2020,293(1):57-69
B-cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long-lasting B-cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long-lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B-cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype-switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B-cell responses to Plasmodium infections. 相似文献
62.
Mischa P. Keizer Angela M. Kamp Nannette Brouwer Marianne D. van de Wetering Diana Wouters Taco W. Kuijpers 《Molecular immunology》2014
MBL-deficiency has been associated with an increased frequency and severity of infection, in particular in children and under immunocompromized conditions. In an open uncontrolled safety and pharmacokinetic MBL-substitution study using plasma-derived MBL (pdMBL) in MBL-deficient pediatric oncology patients, we found that despite MBL trough levels above 1.0 μg/ml MBL functionality was not efficiently restored upon ex vivo testing. 相似文献
63.
Ahmed Ali Elsayed Naoko Asano Koichi Ohshima Koji Izutsu Tomohiro Kinoshita Shigeo Nakamura 《Pathology international》2014,64(7):336-345
To investigate the clinicopathological significance of CD20 expression and Epstein‐Barr virus (EBV) association in Hodgkin and Reed–Sterberg cells of classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in situ hybridization) were investigated in 389 CHL patients in Japan. They included 74 CD20‐positive cases (19%) and 315 CD20‐negative cases (81%). CD20‐positive cases showed significantly older age at onset (P = 0.018) and higher association with EBV (P = 0.002). Multivariate analysis identified EBV‐positivity (but not CD20‐positivity), presence of B symptoms, thrombocytopenia, elevated serum lactate dehydrogenase and performance status >1 as poor prognostic factors for overall survival (OS). We constructed a new prognostic model with these five factors classifying patients into three groups: low risk, 0–1 adverse factor; intermediate risk, 2–3 factors; high risk, 4–5 factors. This prognostic model could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%) classified into the low‐risk group, the 5‐year OS was 91%. For 92 patients (37%) in the intermediate group, the 5‐year OS was 66%; for 11 patients (5%) in the high‐risk group, the 5‐year OS was 36%. In conclusion, EBV is identified as an independent poor prognostic factor for CHL patients. Therefore, examination of EBV association in CHL is recommended as routine pathologic practice especially in countries where EBV infection prevails. 相似文献
64.
�����ȣ�����������ݣ�������־�£���ѧȺ 《中国实用儿科杂志》2014,29(11):849-854
??Abstract??Objective To explore the role of miR-125b in pediatric classical APL?? in order to seek new therapeutic strategies for drug resistant APL. Methods The target genes of miR-125b were predicted online?? validated by Dual-luciferase assay and western blot assay. MiR-125b expression levels were measured in 33 matched-pair APL samples??treated in the First Affiliated Hospital of Sun Yat-sen University and other members of South China Children APL Cooperative Group from March 2007 to September2012??at initial diagnosis and complete remission ??CR?? and in 5 relapsed patients by qRT-PCR. Proliferation and apoptosis were analyzed respectively using the RNA transfection?? MTT assay and flow cytometry. Results The expression of miR-125b was up-regulated in pediatric APL at diagnosis and relapse bone marrow samples?? but returned to normal after complete remission?? miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor Bak1. Remarkably??it was also found to be up-regulated in leukemic drug-resistant cells??NB4-R1??NB4-R2??HL-60/DOX???? and overexpression of exogenous miR-125b could increase their resistance to therapeutic drugs. Conclusion MiR-125b can regulate pediatric classical APL cells proliferation?? apoptosis and drug resistance by repressing BAK1 protein expression. 相似文献
65.
66.
William P. Dempsey Zhuowei Du Anna Nadtochiy Colton D. Smith Karl Czajkowski Andrey Andreev Drew N. Robson Jennifer M. Li Serina Applebaum Thai V. Truong Carl Kesselman Scott E. Fraser Don B. Arnold 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(3)
Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F. Grewe et al., Nature 543, 670–675 (2017); M. T. Rogan, U. V. Stäubli, J. E. LeDoux, Nature 390, 604–607 (1997)], the underlying structural changes at the synapse level remain poorly understood. Here, we capture synaptic changes in the midlarval zebrafish brain that occur during associative memory formation by imaging excitatory synapses labeled with recombinant probes using selective plane illumination microscopy. Imaging the same subjects before and after classical conditioning at single-synapse resolution provides an unbiased mapping of synaptic changes accompanying memory formation. In control animals and animals that failed to learn the task, there were no significant changes in the spatial patterns of synapses in the pallium, which contains the equivalent of the mammalian amygdala and is essential for associative learning in teleost fish [M. Portavella, J. P. Vargas, B. Torres, C. Salas, Brain Res. Bull. 57, 397–399 (2002)]. In zebrafish that formed memories, we saw a dramatic increase in the number of synapses in the ventrolateral pallium, which contains neurons active during memory formation and retrieval. Concurrently, synapse loss predominated in the dorsomedial pallium. Surprisingly, we did not observe significant changes in the intensity of synaptic labeling, a proxy for synaptic strength, with memory formation in any region of the pallium. Our results suggest that memory formation due to classical conditioning is associated with reciprocal changes in synapse numbers in the pallium.It is widely believed that memories are formed as a result of alterations in synaptic connections between axons and dendrites, an idea first proposed by Ramon y Cajal (1–4). Although synapse changes have been extensively studied in brain slices in the context of long-term potentiation (5, 6), less is known about how synapses in a living vertebrate are modified when a memory is formed.Memory formation has been widely studied using classical conditioning (CC), a robust and straightforward form of learning in which an animal is exposed to a neutral stimulus (conditioned stimulus, CS) paired with an appetitive or aversive stimulus (unconditioned stimulus, US) that evokes a specific behavioral response (UR, unconditioned response) (7, 8). As a result of the pairing, animals learn to associate the CS with the US, causing them to respond to the CS with a conditioned response (CR) identical to the UR, signifying memory retrieval (9, 10). Memory retrieval is also evoked by activating a cellular engram, a group of neurons active during memory formation and retrieval (11–18). The central locus of CC in mammals, the amygdala (19), is located in a relatively inaccessible area beneath the cortex (20). Thus, although numerous longitudinal imaging studies have documented experience-dependent changes in the structure of spines of cortical and hippocampal neurons (21, 22), few imaging studies have directly examined synaptic changes that occur in the amygdala during associative memory formation.Instead, synaptic changes that occur in the amygdala during CC (23) have been studied primarily using indirect measures of synaptic strength, such as the ratio of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor/N-methyl D-aspartate (AMPA/NMDA) currents in excitatory postsynaptic currents (EPSCs). Increases in AMPA/NMDA ratio in amygdalar neurons following auditory fear conditioning (FC), a type of CC (24–27), indicate that associative memory formation coincides with increases in synaptic strength. In addition, imaging experiments in brain regions beyond the amygdala have shown diverse effects following CC. For example, following contextual fear conditioning, engram neurons in the CA1 region of the hippocampus that receive inputs from CA3 engram neurons displayed spines that were larger and more densely packed than nonengram cells (28). Furthermore, experiments in which neuronal morphology was directly observed before and after FC found that neurons in the frontal association (29) and primary motor cortex (30) showed a decrease in the number of spines, whereas neurons in the auditory cortex showed an increase in spine number with memory formation (31).To obtain previously unavailable insight into memory formation within the central locus of associative memory storage, we developed a paradigm combining in vivo labeling and imaging with informatics and analysis tools. We used this paradigm to map synaptic changes that occur over time in the intact brain of a living vertebrate during memory formation. We imaged the pallium of teleost fish, which contains the putative homolog of the mammalian amygdala based on anatomy (32), gene expression (33), and function (34). The pallium is on the surface of the brain (35), and zebrafish larvae are highly transparent, allowing for intact, whole-brain imaging using selective plane illumination microscopy (SPIM) without the need for invasive intervention (36). In addition, while most studies of learning in zebrafish have used adults (37–40), at least one study showed that larval zebrafish can learn to associate a place with a positive valence US (41). These attributes suggest that larval zebrafish may be an ideal model organism for studying synaptic changes during memory formation due to CC. We have engaged this challenge by combining purpose-built experimental tools with data management software that enables transparent analyses of large and heterogeneous datasets. All data were characterized and stored at the time of creation in a customized data management system designed to conform to findability, accessibility, interoperability, and reusability (i.e., FAIR principles) (see Materials and Methods) (42). 相似文献
67.
68.
化学计量学结合信息熵赋权优选半夏白术天麻汤提取工艺 总被引:3,自引:2,他引:1
目的建立化学计量学与信息熵赋权相结合的提取工艺优化方法,并将其应用于半夏白术天麻汤水提工艺优化,以充分保证经典名方的有效性和质量一致性。方法以半夏白术天麻汤为模型药物,采用HPLC法建立指纹图谱,对共有峰峰面积进行主成分分析(PCA),以PCA总因子得分、指纹图谱相似度及干膏收率为评价指标,采用L9(34)正交设计法考察加水量、浸泡时间、煎煮时间、煎煮次数对提取效果的影响,信息熵赋权法确定各指标的客观权重,优化水提工艺参数。结果通过中药色谱指纹图谱相似度评价系统匹配26个共有峰,并确定其中7个化合物。根据综合评分结果,确定最佳提取工艺为12倍加水量,煎煮2次,每次1 h。3批验证综合评分均值为0.418 0,RSD为3.32%。结论优选后的工艺提取率高、稳定性和重复性好,适用于半夏白术天麻汤经典名方制剂的工业化生产。 相似文献
69.
目的建立半夏泻心汤水煎液的HPLC指纹图谱,研究处方中黄芩、黄连药材-饮片-全方水煎液的量值传递关系。方法以《伤寒论》中记载的煎煮方法制备半夏泻心汤水煎液,建立半夏泻心汤HPLC指纹图谱,对特征峰进行归属;以转移率、出膏率、指纹图谱的相似度为指标,对处方中黄芩、黄连药材-饮片-全方水煎液的量值传递关系进行分析。结果黄芩中指标性成分黄芩苷从药材到饮片的转移率为81.08%~119.82%;饮片到全方水煎液的黄芩苷的转移率为44.55%~59.05%,黄连中指标性成分小檗碱从药材到饮片的转移为66.65%~97.51%;饮片到全方水煎液的小檗碱的转移率为7.83%~22.93%;全方的出膏率为12.99%~17.21%;15批全方指纹图谱的相似度为0.978~0.999。结论该指纹图谱所建立的质量评价方法适用于黄芩、黄连药材-饮片-全方水煎液质量控制,可为经典名方等质量评价办法的制定提出一定的参考。 相似文献
70.
芍药甘草汤最早见于张仲景《伤寒杂病论》,由白芍和甘草(炙)等比例配伍而成,具有养血敛阴、调和肝脾、缓急止痛之功效,用于血虚津伤和筋脉失濡所致的腿脚挛急、脘腹疼痛。被历代医家推崇并沿用至今,并且拓展出了应用范围。现代药理研究表明,芍药甘草汤具有显著的解痉、止痛、镇咳、平喘及抗炎等作用,用于治疗痉挛性疾病、疼痛性疾病、炎症性疾病、支气管哮喘及妇产科疾病等。笔者从芍药甘草汤的历史沿革与方义衍变、组方配伍分析、药理药效学研究、现代临床应用4个方面进行系统阐述,以期为该经典名方的现代研究开发提供理论依据和文献参考,并为其制剂的临床定位提供理论和实践支撑。 相似文献