全文获取类型
收费全文 | 1027篇 |
免费 | 63篇 |
国内免费 | 4篇 |
专业分类
儿科学 | 25篇 |
妇产科学 | 37篇 |
基础医学 | 157篇 |
口腔科学 | 16篇 |
临床医学 | 88篇 |
内科学 | 274篇 |
皮肤病学 | 52篇 |
神经病学 | 102篇 |
特种医学 | 32篇 |
外科学 | 61篇 |
综合类 | 6篇 |
预防医学 | 72篇 |
眼科学 | 8篇 |
药学 | 93篇 |
中国医学 | 8篇 |
肿瘤学 | 63篇 |
出版年
2023年 | 14篇 |
2022年 | 33篇 |
2021年 | 34篇 |
2020年 | 25篇 |
2019年 | 22篇 |
2018年 | 41篇 |
2017年 | 19篇 |
2016年 | 20篇 |
2015年 | 35篇 |
2014年 | 37篇 |
2013年 | 44篇 |
2012年 | 95篇 |
2011年 | 105篇 |
2010年 | 52篇 |
2009年 | 46篇 |
2008年 | 68篇 |
2007年 | 64篇 |
2006年 | 56篇 |
2005年 | 50篇 |
2004年 | 67篇 |
2003年 | 64篇 |
2002年 | 52篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有1094条查询结果,搜索用时 15 毫秒
81.
Armenise D Muraglia M Florio MA De Laurentis N Rosato A Carrieri A Corbo F Franchini C 《Archiv der Pharmazie》2012,345(5):407-416
As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7‐fluoro‐3,4‐dihydro‐2H‐1,4‐benzothiazine derivatives ( 4a–4f , 4h ) and 7‐fluoro‐2H‐1,4‐benzothiazin‐3(4H)‐one analogues ( 4j–4o ) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram‐positive and Gram‐negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro‐substituted‐2‐amino‐5‐fluorobenzenethiol 6a–6c . The biological screening identified in compounds 4a , 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a–6c . Surprisingly, 6a–6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram‐positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents. 相似文献
82.
Daleen Badenhorst Gauthier Dobigny Filomena Adega Raquel Chaves Patricia C. M. O’Brien Malcolm A. Ferguson-Smith Paul D. Waters Terence J. Robinson 《Chromosome research》2011,19(6):709-727
The Rattini (Muridae, Murinae) includes the biologically important model species Rattus norvegicus (RNO) and represents a group of rodents that are of clinical, agricultural and epidemiological importance. We present a comparative
molecular cytogenetic investigation of ten Rattini species representative of the genera Maxomys, Leopoldamys, Niviventer, Berylmys, Bandicota and Rattus using chromosome banding, cross-species painting (Zoo-fluorescent in situ hybridization or FISH) and BAC-FISH mapping. Our
results show that these taxa are characterised by slow to moderate rates of chromosome evolution that contrasts with the extensive
chromosome restructuring identified in most other murid rodents, particularly the mouse lineage. This extends to genomic features
such as NOR location (for example, NORs on RNO 3 are present on the corresponding chromosomes in all species except Bandicota savilei and Niviventer fulvescens, and the NORs on RNO 10 are conserved in all Rattini with the exception of Rattus). The satellite I DNA family detected and characterised herein appears to be taxon (Rattus) specific, and of recent origin (consistent with a feedback model of satellite evolution). BAC-mapping using clones that
span regions responsible for the morphological variability exhibited by RNO 1, 12 and 13 (acrocentric/submetacentric) and
their orthologues in Rattus species, demonstrated that the differences are most likely due to pericentric inversions as exemplified by data on Rattus tanezumi. Chromosomal characters detected using R. norvegicus and Maxomys surifer whole chromosome painting probes were mapped to a consensus sequence-based phylogenetic tree thus allowing an objective assessment
of ancestral states for the reconstruction of the putative Rattini ancestral karyotype. This is thought to have comprised
46 chromosomes that, with the exception of a single pair of metacentric autosomes, were acrocentric in morphology. 相似文献
83.
The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ~20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity. From a further ~50% of VGF derive multiple "fragments", largely identified in the human cerebro-spinal fluid by proteomic studies searching for disease biomarkers. These represent an important starting point for discovery of further VGF products relevant to neuronal brain functions, as well as to neurodegenerative and psychiatric disease conditions. A distinct feature of VGF peptides is their cell type specific diversity in all neuroendocrine organs studied so far. Selective differential profiles are found across the cell populations of pituitary, adrenal medulla and pancreatic islets, and in gastric neuroendocrine as well as some further mucosal cells, and are yet to be investigated in neuronal systems. At the same time, specific VGF peptide/s undergo selective modulation in response to organ or cell population relevant stimuli. Such pattern argues for a multiplicity of roles for VGF peptides, including endocrine functions, local intercellular communication, as well as the possible mediation of intracellular mechanisms. 相似文献
84.
José Guilherme Tralhão Emir Hoti Bárbara Oliveiros Ana M. Abrantes M. Filomena Botelho F. Castro-Sousa 《World journal of surgery》2009,33(12):2627-2634
Background
Intermittent Pringle maneuver or selective portal clamping often are used to control inflow during parenchymal liver transection. This study was designed to determinate whether these maneuvers are associated with adverse hepatic function. 相似文献85.
86.
87.
Granata R Settanni F Biancone L Trovato L Nano R Bertuzzi F Destefanis S Annunziata M Martinetti M Catapano F Ghè C Isgaard J Papotti M Ghigo E Muccioli G 《Endocrinology》2007,148(2):512-529
Among its pleiotropic actions, ghrelin modulates insulin secretion and glucose metabolism. Herein we investigated the role of ghrelin in pancreatic beta-cell proliferation and apoptosis induced by serum starvation or interferon (IFN)-gamma/TNF-alpha, whose synergism is a major cause for beta-cell destruction in type I diabetes. HIT-T15 beta-cells expressed ghrelin but not ghrelin receptor (GRLN-R), which binds acylated ghrelin (AG) only. However, both unacylated ghrelin (UAG) and AG recognized common high-affinity binding sites on these cells. Either AG or UAG stimulated cell proliferation through Galpha(s) protein and prevented serum starvation- and IFN-gamma/TNF-alpha-induced apoptosis. Antighrelin antibody enhanced apoptosis in either the presence or absence of serum but not cytokines. AG and UAG even up-regulated intracellular cAMP. Blockade of adenylyl cyclase/cAMP/protein kinase A signaling prevented the ghrelin cytoprotective effect. AG and UAG also activated phosphatidyl inositol 3-kinase (PI3K)/Akt and ERK1/2, whereas PI3K and MAPK inhibitors counteracted the ghrelin antiapoptotic effect. Furthermore, AG and UAG stimulated insulin secretion from HIT-T15 cells. In INS-1E beta-cells, which express GRLN-R, AG and UAG caused proliferation and protection against apoptosis through identical signaling pathways. Noteworthy, both peptides inhibited cytokine-induced NO increase in either HIT-T15 or INS-1E cells. Finally, they induced cell survival and protection against apoptosis in human islets of Langerhans. These expressed GRLN-R but showed also UAG and AG binding sites. Our data demonstrate that AG and UAG promote survival of both beta-cells and human islets. These effects are independent of GRLN-R, are likely mediated by AG/UAG binding sites, and involve cAMP/PKA, ERK1/2, and PI3K/Akt. 相似文献
88.
Rindi G Licini L Necchi V Bottarelli L Campanini N Azzoni C Favret M Giordano G D'Amato F Brancia C Solcia E Ferri GL 《The Journal of clinical endocrinology and metabolism》2007,92(7):2811-2815
BACKGROUND: Although the neurotrophin-inducible gene vgf is expressed in mammalian neurons and endocrine cells, limited data is available in man. AIM: The objective of the study was to map proVGF peptides in human endocrine cells during development, adulthood, hyperplasia, and tumors. METHODS: Antisera were generated against peptides related to internal cleavage or cleavage-amidation sites (rat proVGF(422-430) and human proVGF(298-306)-NH2) and the proVGF C-terminal ending (human proVGF(607-615)). Developing and normal adult endocrine cells, hyperplastic endocrine lesions (thyroid, parathyroid, lung, and stomach), and 120 tumors (102 endocrine) were studied. Immunogold electron microscopy was performed on normal adult pancreas and gut, and Western blotting was performed on extracts of control tissues and endocrine tumors. RESULTS: proVGF fragments were revealed in developing pituitary, gut, pancreas, and adrenal medulla from 10 gestational weeks, in normal adult pituitary and adrenal medulla, pancreatic glucagon, and insulin cells and gut serotonin cells, in hyperplastic thyroid calcitonin cells, lung P cells, gastric enterochromaffin-like cells, and gastrin cells, and in 88 of 102 endocrine tumors. At electron microscopy proVGF immunoreactivity was restricted to electron-dense granules. Western blotting revealed large molecular weight forms and cleavage fragments in both control tissues and tumor extracts. CONCLUSIONS: proVGF-related peptides are present in endocrine cells early during development and adulthood and increase in hyperplasia and tumors, and proVGF fragments could be novel diagnostic tools for endocrine cells and related lesions, including tumors. 相似文献
89.
Gomes CM Welling M Que I Henriquez NV van der Pluijm G Romeo S Abrunhosa AJ Botelho MF Hogendoorn PC Pauwels EK Cleton-Jansen AM 《European journal of nuclear medicine and molecular imaging》2007,34(11):1793-1803
Purpose The purpose of this work was the development of an orthotopic model of osteosarcoma based on luciferase-expressing tumour
cells for the in vivo imaging of multidrug resistance (MDR) with 99mTc-sestamibi.
Methods Doxorubicin-sensitive (143B-luc+) and resistant (MNNG/HOS-luc+) osteosarcoma cell lines expressing different levels of P-glycoprotein and carrying a luciferase reporter gene were inoculated
into the tibia of nude mice. Local tumour growth was monitored weekly by bioluminescence imaging and X-ray. After tumour growth,
a 99mTc-sestamibi dynamic study was performed. A subset of animals was pre-treated with an MDR inhibitor (PSC833). Images were
analysed for calculation of 99mTc-sestamibi washout half-life (t
1/2), percentage washout rate (%WR) and tumour/non-tumour (T/NT) ratio.
Results A progressively increasing bioluminescent signal was detected in the proximal tibia after 2 weeks. The t
1/2 of 99mTc-sestamibi was significantly shorter (p < 0.05) in drug-resistant MNNG/HOS-luc+ tumours (t
1/2 = 87.3 ± 15.7 min) than in drug-sensitive 143B-luc+ tumours (t
1/2 = 161.0 ± 47.4 min) and decreased significantly with PSC833 (t
1/2 = 173.0 ± 24.5 min, p < 0.05). No significant effects of PSC833 were observed in 143B-luc+ tumours. The T/NT ratio was significantly lower (p < 0.05) in MNNG/HOS-luc+ tumours than in 143B-luc+ tumours at early (1.55 ± 0.22 vs 2.14 ± 0.36) and delayed times (1.12 ± 0.11 vs 1.62 ± 0.33). PSC833 had no significant effects
on the T/NT ratios of either tumour.
Conclusion The orthotopic injection of tumour cells provides an animal model suitable for functional imaging of MDR. In vivo bioluminescence
imaging allows the non-invasive monitoring of tumour growth. The kinetic analysis of 99mTc-sestamibi washout provides information on the functional activity of MDR related to P-glycoprotein expression and its pharmacological
inhibition in osteosarcoma. 相似文献
90.
Andrea Camerini Sara Donati Paolo Viacava Olimpia Siclari Cheti Puccetti Gianna Tartarelli Chiara Valsuani Filomena De Luca Leonardo Martini Andrea Cavazzana Domenico Amoroso 《Journal of experimental & clinical cancer research : CR》2011,30(1):38