全文获取类型
收费全文 | 6306篇 |
免费 | 487篇 |
国内免费 | 2篇 |
专业分类
6795篇 |
出版年
2023年 | 31篇 |
2022年 | 93篇 |
2021年 | 157篇 |
2020年 | 106篇 |
2019年 | 126篇 |
2018年 | 159篇 |
2017年 | 140篇 |
2016年 | 224篇 |
2015年 | 329篇 |
2014年 | 331篇 |
2013年 | 555篇 |
2012年 | 564篇 |
2011年 | 499篇 |
2010年 | 332篇 |
2009年 | 254篇 |
2008年 | 400篇 |
2007年 | 396篇 |
2006年 | 362篇 |
2005年 | 268篇 |
2004年 | 276篇 |
2003年 | 262篇 |
2002年 | 236篇 |
2001年 | 48篇 |
2000年 | 34篇 |
1999年 | 55篇 |
1998年 | 57篇 |
1997年 | 51篇 |
1996年 | 45篇 |
1995年 | 29篇 |
1994年 | 40篇 |
1993年 | 43篇 |
1992年 | 27篇 |
1991年 | 21篇 |
1990年 | 22篇 |
1989年 | 13篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1986年 | 12篇 |
1985年 | 11篇 |
1984年 | 18篇 |
1983年 | 15篇 |
1982年 | 18篇 |
1981年 | 17篇 |
1980年 | 7篇 |
1978年 | 13篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1972年 | 6篇 |
排序方式: 共有6795条查询结果,搜索用时 15 毫秒
31.
Dario Gastaldi Stefano Morlacchi Roberto Nichetti Claudio Capelli Gabriele Dubini Lorenza Petrini Francesco Migliavacca 《Biomechanics and modeling in mechanobiology》2010,9(5):551-561
The most common approach to treat atherosclerosis in coronary bifurcations is the provisional side-branch (PSB) stenting,
which consists sequentially of the insertion of a stent in the main branch (MB) of the bifurcation and a dilatation of the
side branch (SB) passing through the struts of the stent at the bifurcation. This approach can be followed by a redilatation
of the MB only or by a Final Kissing Balloon (FKB) inflation, both strategies leading to a minor stent distortion in the MB.
The positioning of the stent struts in the bifurcation and the stresses generated in the stent and vessel wall are worthy
of investigation for a better understanding of the mechanobiology of the system. For this purpose, a computer model of an
atherosclerotic coronary bifurcation based on the finite element method was developed; the effects of performing the final
redilatation with the two strategies utilising one or two balloons and those created by a different stent strut positioning
around the SB were investigated. Results correlate well with previous experimental tests regarding the deformation following
balloon expansion. Furthermore, results confirm firstly that the re-establishment of an optimal spatial configuration of the
stent after the PSB approach is achieved with both strategies; secondly, results show that case of stent positioning with
one cell placed centrally (with regard to the SB) should be preferred, avoiding the presence of struts inside the vessel lumen,
which may reduce hemodynamic disturbances. The central positioning also resulted in a better solution in terms of lower stresses
in the stent struts and, more importantly, in the vascular tissues. 相似文献
32.
Brigotti M Carnicelli D Arfilli V Rocchi L Ricci F Pagliaro P Tazzari PL Vara AG Amelia M Manoli F Monti S 《The Journal of biological chemistry》2011,286(40):34514-34521
Shiga toxins (Stx) play an important role in the pathogenesis of hemolytic uremic syndrome, a life-threatening renal sequela of human intestinal infection caused by specific Escherichia coli strains. Stx target a restricted subset of human endothelial cells that possess the globotriaosylceramide receptor, like that in renal glomeruli. The toxins, composed of five B chains and a single enzymatic A chain, by removing adenines from ribosomes and DNA, trigger apoptosis and the production of pro-inflammatory cytokines in target cells. Because bacteria are confined to the gut, the toxins move to the kidney through the circulation. Polymorphonuclear leukocytes (PMN) have been indicated as the carriers that "piggyback" shuttle toxins to the kidney. However, there is no consensus on this topic, because not all laboratories have been able to reproduce the Stx/PMN interaction. Here, we demonstrate that conformational changes of Shiga toxin 1, with reduction of α-helix content and exposition to solvent of hydrophobic tryptophan residues, cause a loss of PMN binding activity. The partially unfolded toxin was found to express both enzymatic and globotriaosylceramide binding activities being fully active in intoxicating human endothelial cells; this suggests the presence of a distinct PMN-binding domain. By reviewing functional and structural data, we suggest that A chain moieties close to Trp-203 are recognized by PMN. Our findings could help explain the conflicting results regarding Stx/PMN interactions, especially as the groups reporting positive results obtained Stx by single-step affinity chromatography, which could have preserved the correct folding of Stx with respect to more complicated multi-step purification methods. 相似文献
33.
Here mitochondrial morphology and dynamics were investigated in Medicago truncatula cell-suspension cultures during growth and senescence. Cell biology techniques were used to measure cell growth and death in culture. Mitochondrial morphology was investigated in vivo using a membrane potential sensor probe coupled with confocal microscopy. Expression of a senescence-associated gene (MtSAG) was evaluated in different cell-growth phases. Mitochondria appeared as numerous, punctuate organelles in cells at the beginning of the subculture cycle, while interconnected networks were observed in actively growing cells. In senescent cells, giant mitochondria were associated with dying cells. The release of cytochrome c from mitochondria was detected in different growth phases of cultured cells. Studies on plant cell cultures allowed us to identify physiological and molecular markers of senescence and cell death, and to associate distinct mitochondrial morphology with cells under different physiological conditions. 相似文献
34.
35.
Cohn RD van Erp C Habashi JP Soleimani AA Klein EC Lisi MT Gamradt M ap Rhys CM Holm TM Loeys BL Ramirez F Judge DP Ward CW Dietz HC 《Nature medicine》2007,13(2):204-210
Skeletal muscle has the ability to achieve rapid repair in response to injury or disease. Many individuals with Marfan syndrome (MFS), caused by a deficiency of extracellular fibrillin-1, exhibit myopathy and often are unable to increase muscle mass despite physical exercise. Evidence suggests that selected manifestations of MFS reflect excessive signaling by transforming growth factor (TGF)-beta (refs. 2,3). TGF-beta is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF-beta signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown. Here we show that increased TGF-beta activity leads to failed muscle regeneration in fibrillin-1-deficient mice. Systemic antagonism of TGF-beta through administration of TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy. 相似文献
36.
37.
Airoldi C Zona C Sironi E Colombo L Messa M Aurilia D Gregori M Masserini M Salmona M Nicotra F La Ferla B 《Journal of biotechnology》2010,156(4):317-324
Curcumin derivatives with high chemical stability, improved solubility and carrying a functionalized appendage for the linkage to other entities, have been synthesized in a straightforward manner. All compounds retained Curcumin ability to bind Aβ peptide oligomers without inducing their aggregation. Moreover all Curcumin derivatives were able to stain very efficiently Aβ deposits. 相似文献
38.
Protein and peptide arrays: recent trends and new directions 总被引:3,自引:0,他引:3
Microarrays of proteins and peptides make it possible the screening of thousands of binding events in a parallel and high throughput fashion; therefore they are emerging as a powerful tool for proteomics and clinical assays. The complex nature of Proteome, the wide dynamic range of protein concentration in real samples and the critical role of immobilized protein orientation must be taken into account to maximize the utility of protein microarrays. Immobilization strategy and designing of an ideal local chemical environment on the solid surface are both essential for the success of a protein microarray experiment. This review article will focus on protein and peptide arrays highlighting their technical challenges and presenting new directions by means of a set of selected recent applications. 相似文献
39.
Michele Carbonelli Chiara La Morgia Giacomo Savini Maria Lucia Cascavilla Enrico Borrelli Filipe Chicani Carolina do V. F. Ramos Solange R. Salomao Vincenzo Parisi Jerry Sebag Francesco Bandello Alfredo A. Sadun Valerio Carelli Piero Barboni 《PloS one》2015,10(6)
Purpose
To investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).Methods
All patients with molecularly confirmed MON, i.e. Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.Results
MM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.Conclusion
The prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces. 相似文献40.
Fabrizi F Mincione F Somma T Scozzafava G Galassi F Masini E Impagnatiello F Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2012,27(1):138-147
The clinically used sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma. 相似文献