全文获取类型
收费全文 | 351篇 |
免费 | 22篇 |
国内免费 | 41篇 |
出版年
2023年 | 10篇 |
2022年 | 13篇 |
2021年 | 15篇 |
2020年 | 10篇 |
2019年 | 17篇 |
2018年 | 17篇 |
2017年 | 10篇 |
2016年 | 14篇 |
2015年 | 24篇 |
2014年 | 34篇 |
2013年 | 67篇 |
2012年 | 24篇 |
2011年 | 23篇 |
2010年 | 18篇 |
2009年 | 10篇 |
2008年 | 9篇 |
2007年 | 10篇 |
2006年 | 12篇 |
2005年 | 11篇 |
2004年 | 12篇 |
2003年 | 9篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有414条查询结果,搜索用时 578 毫秒
1.
《European journal of cell biology》2019,98(5-8):151044
Cripto-1 is a protein participating in tissue orientation during embryogenesis but has also been implicated in a wide variety of cancers, such as colon, lung and breast cancer. Cripto-1 plays a role in the regulation of different pathways, including TGF-β/Smad and Wnt/β-catenin, which are highly associated with cell migration both during embryonal development and cancer progression. Little is known about the detailed subcellular localization of cripto-1 and how it participates in the directional movement of cells. In this study, the subcellular localization of cripto-1 in glioblastoma cells was investigated in vitro with high-resolution microscopy techniques. Cripto-1 was found to be localized to dynamic and shed filopodia and transported between cells through tunneling nanotubes. Our results connect the refined subcellular localization of cripto-1 to its functions in cellular orientation and migration. 相似文献
2.
Two novel ent-atisane type diterpenoids possessing the extra unusal 2-oxopropyl moiety (1 and 2) and four known analogues have been isolated from the roots of Euphorbia ebracteolata. The structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography, 13C NMR calculation, and electronic circular dichroism spectra calculation. Compounds 1 and 2 are the first examples of natural products with ent-atisane type diterpenoids possessing 2-oxopropyl skeleton. Compounds 2, 3, 5, and 6 show antiviral activities against human rhinovirus 3, with IC50 values of 25.27–90.35 μM. Compounds 5 and 6 showed moderate antiviral activities against EV71 at a concentration of 100 μM. 相似文献
3.
本文报道了从我国手足口病(HFMD)患者疱液中肠道病毒71(E71)型H株的分离和鉴定。该株病毒可在原代人胚肺(HEL)细胞、MA104细胞、BSC细胞中生长繁殖,导致典型的肠道病毒CPE出现。将H株接种乳鼠后出现肢体麻痹、第6天开始死亡。电镜下可见感染H株的BSC细胞胞浆中出现大量的结晶状排列的成熟病毒颗粒,直径约25nm。患者双份血清中有对H株4倍增高的中和抗体存在。采用100抗体单位的抗Cox A5、7、9、16、E70、E71抗体和50抗体单位的LBM组合血清A-H以及抗E71BrCr株MeAb P27对H株进行中和试验时,H株可被抗E71血清和MeAb P27所中和。抗E71抗体对H株的最低有效中和作用为1.6抗体单位,MeAb P27对H株的有效中和作用是64抗体单位。其它血清则无此中和作用。然而,在鉴定过程中发现,高滴度的抗Cox A16抗体(200抗体单位以上)也显出有中和H株的作用,提示我们所分离的H株含有与Cox A16的型间共同抗原。 相似文献
4.
5.
Marianne Borloo Koen Augustyns Alexander Belyaev Ingrid de Meester Anne-Marie Lambeir Filip Goossens Willy Bollaert Padinchare Rajan Simon Scharpé Achiel Haemers 《Letters in Peptide Science》1995,2(3-4):198-202
Summary A series of azaproline dipeptides with various N-substituents were synthesized as possible active-site-directed inhibitors of two proline-specific serine proteases, dipeptidyl peptidase IV and prolyl oligopeptidase. Compounds with semicarbazide, carbazate, acylhydrazine and sulphonylhydrazine structures were tested. Some compounds show moderate activity, i.e., in the millimolar range. 相似文献
6.
《Bioorganic & medicinal chemistry》2020,28(12):115551
We describe here the design, synthesis, and evaluation of a macrocyclic peptidomimetic as a potent agent targeting enterovirus A71 (EV71). The compound has a 15-membered macrocyclic ring in a defined conformation. Yamaguchi esterification reaction was used to close the 15-membered macrocycle instead of the typical Ru-catalyzed ring-closing olefin metathesis reaction. The crystallographic characterization of the complex between this compound and its target, 3C protease from EV71, validated the design and paved the way for the generation of a new series of anti-EV71 agents. 相似文献
7.
Nami Masubuchi Yuichi Shidoh Shunzo Kondo Jun Takatoh Kazunori Hanaoka 《Experimental Animals》2013,62(3):211-217
Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscle
degenerative disorder that causes dilated cardiomyopathy in the second decade of life in
affected males. Dystrophin, the gene responsible for DMD, encodes
full-length dystrophin and various short dystrophin isoforms. In the mouse heart,
full-length dystrophin Dp427 and a short dystrophin isoform, Dp71, are expressed. In this
study, we intended to clarify the functions of these dystrophin isoforms in DMD-related
cardiomyopathy. We used two strains of mice: mdx mice, in which Dp427 was
absent but Dp71 was present, and DMD-null mice, in which both were
absent. By immunohistochemical staining and density-gradient centrifugation, we found that
Dp427 was located in the cardiac sarcolemma and also at the T-tubules, whereas Dp71 was
specifically located at the T-tubules. In order to determine whether T tubule-associated
Dp71 was involved in DMD-related cardiac disruption, we compared the cardiac phenotypes
between DMD-null mice and mdx mice. Both
DMD-null mice and mdx mice exhibited severe necrosis,
which was followed by fibrosis in cardiac muscle. However, we could not detect a
significant difference in myocardial fibrosis between mdx mice and
DMD-null mice. Based on the present results, we have shown that cardiac
myopathy is caused predominantly by a deficiency of full-length dystrophin Dp427. 相似文献
8.
Debajit Saha Kevin Leong Nalin Katta Baranidharan Raman 《Journal of visualized experiments : JoVE》2013,(71)
Detection and interpretation of olfactory cues are critical for the survival of many organisms. Remarkably, species across phyla have strikingly similar olfactory systems suggesting that the biological approach to chemical sensing has been optimized over evolutionary time1. In the insect olfactory system, odorants are transduced by olfactory receptor neurons (ORN) in the antenna, which convert chemical stimuli into trains of action potentials. Sensory input from the ORNs is then relayed to the antennal lobe (AL; a structure analogous to the vertebrate olfactory bulb). In the AL, neural representations for odors take the form of spatiotemporal firing patterns distributed across ensembles of principal neurons (PNs; also referred to as projection neurons)2,3. The AL output is subsequently processed by Kenyon cells (KCs) in the downstream mushroom body (MB), a structure associated with olfactory memory and learning4,5. Here, we present electrophysiological recording techniques to monitor odor-evoked neural responses in these olfactory circuits.First, we present a single sensillum recording method to study odor-evoked responses at the level of populations of ORNs6,7. We discuss the use of saline filled sharpened glass pipettes as electrodes to extracellularly monitor ORN responses. Next, we present a method to extracellularly monitor PN responses using a commercial 16-channel electrode3. A similar approach using a custom-made 8-channel twisted wire tetrode is demonstrated for Kenyon cell recordings8. We provide details of our experimental setup and present representative recording traces for each of these techniques. 相似文献
9.
Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography1, confocal scanning laser ophthalmoscopy (cSLO)2, and optical coherence tomography (OCT)3, have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies.Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity4-7 . In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts 6,7. More importantly, based on the well-developed spectroscopic photoacoustic imaging5,8 , PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases 9 such as diabetic retinopathy and neovascular age-related macular degeneration.Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts6,10 . In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented. 相似文献
10.
Anna U. Eriksson Christoffer Svensson Andreas H?rnblad Abbas Cheddad Elena Kostromina Maria Eriksson Nils Norlin Antonello Pileggi James Sharpe Fredrik Georgsson Tomas Alanentalo Ulf Ahlgren 《Journal of visualized experiments : JoVE》2013,(71)
By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen''s (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans. 相似文献