全文获取类型
收费全文 | 490篇 |
免费 | 15篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 4篇 |
妇产科学 | 1篇 |
基础医学 | 70篇 |
口腔科学 | 2篇 |
临床医学 | 26篇 |
内科学 | 68篇 |
皮肤病学 | 17篇 |
神经病学 | 12篇 |
特种医学 | 19篇 |
外科学 | 5篇 |
综合类 | 38篇 |
预防医学 | 68篇 |
眼科学 | 1篇 |
药学 | 154篇 |
中国医学 | 21篇 |
肿瘤学 | 1篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 14篇 |
2016年 | 14篇 |
2015年 | 5篇 |
2014年 | 12篇 |
2013年 | 25篇 |
2012年 | 22篇 |
2011年 | 44篇 |
2010年 | 26篇 |
2009年 | 32篇 |
2008年 | 38篇 |
2007年 | 33篇 |
2006年 | 38篇 |
2005年 | 24篇 |
2004年 | 32篇 |
2003年 | 31篇 |
2002年 | 14篇 |
2001年 | 13篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有511条查询结果,搜索用时 15 毫秒
1.
《L'évolution Psychiatrique》2022,87(1):63-73
GoalsStarting from the example of the exostosis of the external auditory canal, a modification due to the impact of the sea on the body, this article considers how this pathology is experienced and interpreted by those who contract it. After defining “surfer's ear” from an anthropo-medical point of view, we will address the meaning that individuals give to it, such as the belief of becoming fish.MethodologyOver the course of several years of field observation and interviews, mainly on the beaches of the Atlantic Pyrenees, we were able to compare different individuals’ discourses about how the surfing body, immersed in nature, is perceived and experienced.ResultsThis helps to understand thoughts that can link people to the ocean, and more widely to nature, in our contemporary Western society. Thus, penetrating and being penetrated by this living water implies a sensual relationship with the environment, in a search both for erotic pleasure and an enveloping maternal security, lost from birth.DiscussionThis relationship to the environment implements a sensory ecology where the human becomes nature, and nature takes human form. This is an occasion for the reinvention of links, not in an opposition between human and non-human, but by reminding humans that they can find balance in abandoning themselves to nature.ConclusionPathologies of the ear define an imaginary clinic of the body. The body is thus rendered unfit by the physical sensations of marine pathology but, above all, by the belief in a psychic envelopment in water. 相似文献
2.
3.
根据GB/T 12457中氯化钠的测定,针对海参提取物的样品特性,进行煮制法、沉淀蛋白法和灰化法三种前处理改进,再直接滴定法测定样品中的盐分含量。通过实验对比,得出灰化法操作简便、测量结果准确度高等优点,适用于海参胶囊中盐分的测定,对样品能起到控制盐分的目的。 相似文献
4.
Ruiming Zhao Hui Dai Netanel Mendelman Luis G. Cuello Jordan H. Chill Steve A. N. Goldstein 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(50):E7013-E7021
Peptide neurotoxins are powerful tools for research, diagnosis, and treatment of disease. Limiting broader use, most receptors lack an identified toxin that binds with high affinity and specificity. This paper describes isolation of toxins for one such orphan target, KcsA, a potassium channel that has been fundamental to delineating the structural basis for ion channel function. A phage-display strategy is presented whereby ∼1.5 million novel and natural peptides are fabricated on the scaffold present in ShK, a sea anemone type I (SAK1) toxin stabilized by three disulfide bonds. We describe two toxins selected by sorting on purified KcsA, one novel (Hui1, 34 residues) and one natural (HmK, 35 residues). Hui1 is potent, blocking single KcsA channels in planar lipid bilayers half-maximally (Ki) at 1 nM. Hui1 is also specific, inhibiting KcsA-Shaker channels in Xenopus oocytes with a Ki of 0.5 nM whereas Shaker, Kv1.2, and Kv1.3 channels are blocked over 200-fold less well. HmK is potent but promiscuous, blocking KcsA-Shaker, Shaker, Kv1.2, and Kv1.3 channels with Ki of 1–4 nM. As anticipated, one Hui1 blocks the KcsA pore and two conserved toxin residues, Lys21 and Tyr22, are essential for high-affinity binding. Unexpectedly, potassium ions traversing the channel from the inside confer voltage sensitivity to the Hui1 off-rate via Arg23, indicating that Lys21 is not in the pore. The 3D structure of Hui1 reveals a SAK1 fold, rationalizes KcsA inhibition, and validates the scaffold-based approach for isolation of high-affinity toxins for orphan receptors.Venomous animals produce neurotoxic peptides for defense and to capture prey. With potencies in the nanomolar range, the peptides act by modulating the function of target receptors. Toxins isolated from venoms have been used to identify and purify ion channels, to clarify their roles in physiology, to elucidate the structural basis for their function, and, recently, to diagnose and treat disease. Given their utility, it is frustrating that natural toxins cross-react with related receptors (or have no known target) and that most receptors lack a specific, high-affinity toxin. This state of affairs is easily understood; the small amounts of toxins isolated from natural sources makes target identification a challenge and their purpose in the wild does not favor target specificity. Here, we advance our approach to overcoming these problems, that is, creation of expression libraries of toxins allowing cloning based on target binding (1), by seeking a specific, high-affinity ligand for an orphan channel receptor.Our strategy is to start with a known toxin and to design a phage-display library using the genetic database of its predicted homologs, in native and combinatorial fashion, so the encoded peptides share the same structural scaffold. As a proof of concept, we previously addressed a case of inadequate target discrimination by known natural toxins using a library of ∼11,200 peptides designed to share the fold in α-KTx scorpion toxins and a specific ligand for the human voltage-gated potassium channel Kv1.3 was isolated (1). Moka1, composed of domains from three scorpion species, blocks Kv1.3 with nanomolar affinity, allowing it to suppress T-cell-mediated immune responses, and is without unwanted side effects on gastrointestinal motility seen with natural toxins because it does not cross-inhibit Kv1.1 and Kv1.2. Supporting the design premise that encoded peptides are expressed, correctly folded, and accessible on the phage surface in a manner permissive of sorting based on target binding, the determined 3D structure of Moka1 revealed it to be constructed on an α-KTx scaffold. Here, we sought to extend our strategy by testing another scaffold and creation of a library sufficiently large to achieve isolation of peptides specific for a target with no known ligand.KcsA is a prokaryotic channel with high potassium conductance and selectivity (2). The first potassium channel visualized at high resolution (3), KcsA has a single ion conduction pathway on the central axis of symmetry formed by four identical subunits, each with two transmembrane segments and a reentrant pore-forming loop (TM1-P-TM2). The 3D structure of KcsA confirmed explanations for selective ion permeation and conduction pathway gating deduced in the period before crystallization and its continued interrogation has been key to delineating the mechanistic bases for channel function (4–6). Although described 20 y ago (7), KcsA remains an orphan target so that studies with peptide toxins have required production of mutant channels with multiple mutations in the pore domain (8) or chimeras such as Kv1.3-KcsA, where the entire KcsA pore domain is replaced by the one in Kv1.3 (9).To isolate toxins for KcsA, a peptide library was designed with ∼1,562,750 variants via combinatorial permutation of sequences related to the sea anemone type I (SAK1) toxin ShK. Phage sorting was performed on purified, wild-type KcsA channels. Peptides expressed on the enriched phage were synthesized and studied by surface plasmon resonance (SPR) to characterize their binding to purified KcsA and by voltage-clamp electrophysiology to assess channel blockade. Hui1, a novel and specific inhibitor of KcsA, HmK, a natural and promiscuous blocker, and Hui1 mutants were evaluated to identify toxin segments and residues responsible for specificity and affinity and to discern the mechanism of channel inhibition. The 3D structure of Hui1 determined by NMR, the 1:1 stoichiometry of KcsA inhibition via a pore-directed mechanism, and the role of two, canonical “dyad” residues (Lys21 and Tyr22) in high-affinity binding all met expectations for a SAK1-type toxin. In contrast, the influence of permeant trans ions (those traversing the channel after entering from the opposite side of the membrane) on dissociation of Hui1 from its external binding site indicated that Arg23, a residue with a side chain too bulky to fit snugly into the potassium conduction pore (10), was responsible for the voltage dependence of block rather than Lys21. This unexpected role for Hui1-Arg23 could reflect a new SAK1 binding orientation for the novel toxin; however, some models have located the ShK dyad Lys in the outer pore vestibule of Kv1.3 (11) rather than in the narrow portion of the conduction pathway (12). We posit that Hui1 binds and blocks like some, and perhaps most, natural SAK1 toxins. 相似文献
5.
Craig Baker-Austin Joaquin A. Trinanes Saara Salmenlinna Margareta L?fdahl Anja Siitonen Nick G.H. Taylor Jaime Martinez-Urtaza 《Emerging infectious diseases》2016,22(7):1216-1220
During summer 2014, a total of 89 Vibrio infections were reported in Sweden and Finland, substantially more yearly infections than previously have been reported in northern Europe. Infections were spread across most coastal counties of Sweden and Finland, but unusually, numerous infections were reported in subarctic regions; cases were reported as far north as 65°N, ≈100 miles (160 km) from the Arctic Circle. Most infections were caused by non-O1/O139 V. cholerae (70 cases, corresponding to 77% of the total, all strains were negative for the cholera toxin gene). An extreme heat wave in northern Scandinavia during summer 2014 led to unprecedented high sea surface temperatures, which appear to have been responsible for the emergence of Vibrio bacteria at these latitudes. The emergence of vibriosis in high-latitude regions requires improved diagnostic detection and clinical awareness of these emerging pathogens. 相似文献
6.
In this study, the carbonic anhydrase (CA) enzyme was purified from Black Sea trout (Salmo trutta Labrax Coruhensis) kidney with a specific activity of 603.77 EU/mg and a yield of 35.5% using Sepharose-4B-l-tyrosine- sulphanilamide affinity column chromatography. For determining the enzyme purity and subunit molecular mass, sodiumdodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was performed and single band was observed. The molecular mass of subunit was found approximately 29.71 kDa. The optimum temperature, activation energy (Ea), activation enthalpy (ΔH) and Q10 values were obtained from Arrhenius plot. Km and Vmax values for p-nitrophenyl acetate of the purified enzyme were calculated from Lineweaver-Burk graphs. In addition, the inhibitory effects of different heavy metal ions (Fe2+, Pb2+, Co2+, Ag+ and Cu2+) on Black Sea trout kidney tissue CA enzyme activities were investigated by using esterase method under in vitro conditions. The heavy metal concentrations inhibiting 50% of enzyme activity (IC50) were obtained. Finally Ki values and inhibition types were calculated from Lineweaver-Burk graphs. 相似文献
7.
目的 了解2013-2018年山东省食品中镉污染状况。方法 2013-2018年在山东省范围内应用完全随机采样法采集市售18类28 867份食品,按照国家标准操作程序进行实验室检测。结果 镉含量合格率为98.85%(28 535/28 867)。镉含量较高的食品为藻类、水产品、坚果及籽类和食用菌,均值分别为0.7085 mg/kg、0.2656 mg/kg、0.0633 mg/kg和0.0633 mg/kg;镉含量较低的食品为饮料酒类、乳类和水果类,均值分别为0.0021 mg/kg、0.0027 mg/kg和0.0030 mg/kg。408份海蟹的镉检出率为92.89%(379/408),超标率为42.65%(174/408),蟹膏、蟹黄镉超标率分别为90.24%、82.86%,最高超标38.80倍。结论 山东省市售食品镉超标率较低。水产品特别是海蟹的蟹膏、蟹黄部分超标严重,建议居民谨慎食用海蟹蟹膏、蟹黄。 相似文献
8.
Nanoparticles have found use in a wide range of applications, mainly as carriers of active biomolecules. It is thus necessary to assess their toxicity for human health, as well as for the environment, on which there is still a gap of knowledge. In this work, sea urchin Paracentrotus lividus, a widely used model for embryotoxicity and spermiotoxicity, has been used to assess potential detrimental effects of amino-functionalized mesoporous silica nanoparticles (NH2-MSiNPs) on embryonic development. Specifically, gametes quality, embryogenesis morphological and timing alterations, and cellular stress markers, such as mitochondrial functionality, were assessed in presence of different concentrations of NH2-MSiNPs in filtered seawater (FSW). Furthermore, dorsal-ventral axis development and skeletogenesis were characterized by microscopy imaging and gene expression analysis. NH2-MSiNPs determined a strong reduction in the egg fertilization rate. Consequently, the presence of NH2-MSiNPs resulted detrimental in P. lividus embryonic development, with severe morphological alterations correlated with an increased embryos mortality. Finally, NH2-MSiNPs treatment was responsible for other toxic effects, such as reduced mitochondrial function and skeletogenesis alterations, according to the reduced mineralization sites in the endoskeleton formation and the related genes altered expression. Taken together, these results suggest the potential toxic effects of NH2-MSiNPs on the marine ecosystem, with consequences for the development and reproduction of its organisms. Despite their promising potential as carriers of biomolecules, it is pivotal to consider that their uncontrolled use may result harmful to the environment and, consequently, to living organisms. 相似文献
9.
Climate change would have a range of impacts on human health. Health impacts would be caused by the direct effect of climatic factors on human health, such as heat stress, and possible changes in the frequency and intensity of extreme weather events such as storms, floods and droughts. Impacts on health would also be mediated by the indirect effects of climate change, such as changes in availability of food and water and the distribution of vector‐borne diseases. The majority of health impacts would be adverse and would depend greatly on the vulnerability of populations. 相似文献
10.
孔佳 《现代中西医结合杂志》2012,21(6):587-588,599
目的探讨复方海蛇胶囊(RSC)联合盐酸多奈哌齐治疗阿尔茨海默病(AD)的有效性及安全性。方法 96例AD患者随机分为RSC组30例、盐酸多奈哌齐组32例和联合用药组34例,RSC组给予复方海蛇胶囊口服;盐酸多奈哌齐组给予盐酸多奈哌齐口服;联合用药组同时口服复方海蛇胶囊和盐酸多奈哌齐;连续用药6个月。观察3组患者治疗前后智能状态量表(MMSE)、日常生活能力量表(ADL)、认知次级量表(ADAS-Cog)、痴呆程度评定量表(CDR)以及副反应量表(TESS)评定情况。结果治疗后各组MMSE评分均大于治疗前(P<0.05),ADL、ADAS-Cog、CDR评分均小于治疗前(P均<0.05);3组不良反应发生率比较无显著性差异(P>0.05)。结论复方海蛇胶囊联合盐酸多奈哌齐治疗AD安全、有效,疗效优于单一药物,且不良反应发生率低。 相似文献