全文获取类型
收费全文 | 1348篇 |
免费 | 151篇 |
专业分类
1499篇 |
出版年
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 43篇 |
2020年 | 14篇 |
2019年 | 31篇 |
2018年 | 44篇 |
2017年 | 37篇 |
2016年 | 50篇 |
2015年 | 70篇 |
2014年 | 57篇 |
2013年 | 75篇 |
2012年 | 67篇 |
2011年 | 86篇 |
2010年 | 50篇 |
2009年 | 63篇 |
2008年 | 74篇 |
2007年 | 76篇 |
2006年 | 51篇 |
2005年 | 54篇 |
2004年 | 50篇 |
2003年 | 60篇 |
2002年 | 46篇 |
2001年 | 39篇 |
2000年 | 40篇 |
1999年 | 31篇 |
1998年 | 21篇 |
1997年 | 12篇 |
1996年 | 17篇 |
1995年 | 19篇 |
1994年 | 10篇 |
1993年 | 16篇 |
1992年 | 10篇 |
1991年 | 14篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 14篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1967年 | 6篇 |
排序方式: 共有1499条查询结果,搜索用时 0 毫秒
151.
Pérez-Uribe A Molina de Soschin D Arenas R Reyes M 《Revista iberoamericana de micología》2005,22(2):118-121
Primary cutaneous mucormycosis is an unusual mycotic infection associated to immunosupression. We present a 34 year-old woman with HIV infection with a necrotic primary mucormycosis of the skin associated to a venous catheter. She was treated with amphotericin B and surgical debridement. 相似文献
152.
153.
Molina J Stumpner A 《Journal of experimental zoology. Part A, Comparative experimental biology》2005,303(12):1085-1103
Soma-ipsilateral branches of the large segmental omega neuron of the phaneropterid bush cricket Ancistrura nigrovittata have smooth endings, which extend through most of the auditory neuropile. Correspondingly, it shows a broad frequency tuning. Large excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) are observed when recording from soma-ipsilateral branches. Stimulation from the soma-ipsilateral side leads to a strong excitation. Soma-contralateral branches have a strong, beaded appearance. IPSPs, which seem to be of soma-contralateral origin, can be recorded from these branches. Stimulation from the soma-contralateral side leads to a strong inhibition of the omega neuron. Soma-contralateral stimulation must be 30-40 dB more intense than soma-ipsilateral stimulation to evoke similar spike numbers in the omega neuron. The side-to-side difference is reduced to 10-15 dB after cutting the input from the soma-contralateral leg (tympanic nerve). The thresholds for eliciting IPSPs by soma-contralateral stimulation correspond roughly to excitatory thresholds of the mirror-image omega with the same stimuli. Pharmacological treatment with picrotoxin (PTX) or photoinactivation of the Lucifer Yellow filled mirror-image omega neuron reduces contralateral inhibition considerably and eliminates all visible IPSPs. Nevertheless, an additional contralateral inhibition survives both procedures and is only eliminated after cutting the soma-contralateral tympanic nerve. These results demonstrate that the mirror-image partners of the omega neuron mutually inhibit each other in bush crickets--as in crickets. This mutual inhibition is PTX-sensitive. At least one additional element exerts contralateral PTX-insensitive inhibition on the omega neuron. 相似文献
154.
Vila-Perelló M Sánchez-Vallet A García-Olmedo F Molina A Andreu D 《The Journal of biological chemistry》2005,280(2):1661-1668
The increasing occurrence of bacterial resistance to antibiotics is driving a renewed interest on antimicrobial peptides, in the hope that understanding the structural features responsible for their activity will provide leads into new anti-infective drug candidates. Most chemical studies in this field have focused on linear peptides of various eukaryotic origins, rather than on structures with complex folding patterns found also in nature. We have undertaken the structural dissection of a highly knotted, cysteine-rich plant thionin, with the aim of defining a minimal, synthetically accessible, structure that preserves the bioactive properties of the parent peptide. Using efficient strategies for directed disulfide bond formation, we have prepared a substantially simplified (45% size reduction) version with undiminished antimicrobial activity against a representative panel of pathogens. Analysis by circular dichroism shows that the downsized peptide preserves the central double alpha-helix of the parent form as an essential bioactive motif. Membrane permeability and surface plasmon resonance studies confirm that the mechanism of action remains unchanged. 相似文献
155.
This article reports the kinetic determination of 6-methoxy-2-naphthylacetic acid (6-MNA), the major metabolite of nabumetone, from micelle-stabilized room temperature phosphorescence (MS-RTP) measurements made by using the stopped-flow mixing technique. This methodology allows one to determine analytes in complex matrices without the need for a tedious separation process. It also shortens analysis times substantially. The proposed method uses simplex methodology to optimize the chemical and instrumental variables affecting the phosphorescence. It was applied to the determination of 6-MNA in human urine. The maximum phosphorescence signal is obtained within only 10 s after the sample is prepared. The maximum slope of the kinetic curve, which corresponds to the maximum rate of the phosphorescence development, is measured at lambda(ex)=273 nm and lambda(em)=516 nm. Least-squares regression was used to fit experimental data, and the detection limit, repeatability, and standard deviation for replicate samples were determined. 相似文献
156.
Seasonal environmental changes regulate the expression of the histone variant macroH2A in an eurythermal fish 总被引:2,自引:0,他引:2
Pinto R Ivaldi C Reyes M Doyen C Mietton F Mongelard F Alvarez M Molina A Dimitrov S Krauskopf M Vera MI Bouvet P 《FEBS letters》2005,579(25):5553-5558
Adaptation to cold and warm conditions requires dramatic change in gene expression. The acclimatization process of the common carp Cyprinus carpio L. in its natural habitat has been used to study how organisms respond to natural environmental changes. At the cellular level, adaptation to cold condition is accompanied by a dramatic alteration in nucleolar structure and a down regulation of the expression of ribosomal genes. We show that the enrichment of condensed chromatin in winter adapted cells is not correlated with an increase of the heterochromatin marker trimethyl and monomethyl K20H4. However, the expression of the tri methyl K4 H3 and of the variant histone macroH2A is significantly increased during the winter season together with a hypermethylation of CpG residues. Taking into account the properties of macroH2A toward chromatin structure and dynamics and its role in gene repression our data suggest that the increased expression of macroH2A and the hypermethylation of DNA which occurs upon winter-acclimatization plays a major role for the reorganization of chromatin structure and the regulation of gene expression during the physiological adaptation to a colder environment. 相似文献
157.
Spitzer D Unsinger J Mao D Wu X Molina H Atkinson JP 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(11):7763-7770
Because of the complement system's involvement in many human diseases and potential complications associated with its systemic blockade, site-specific regulation of this effector system is an attractive concept. We report on further developments of such an approach using a single-chain Ab fragment as a vehicle to deliver complement regulatory proteins to a defined cell type. In a model system in which RBCs deficient in complement receptor 1-related gene/protein y (Crry) are rapidly cleared after injection into wild-type animals by a complement-dependent mechanism, we selectively reconstituted these cells with N- and C-terminally targeted recombinant forms of Crry. Transfusion of Crry-coated knockout RBCs into C57BL/6 mice extended their in vivo half-life from <5 min to approximately 2 days. Maintenance of protective levels of Crry (by a combined treatment of donor and recipient RBCs) led to nearly normal RBC survival. Uniform in vitro and in vivo coating of the RBCs and the more efficient complement inhibitory capacity of C-terminally tagged Crry were other interesting features of this experimental system. These results suggest the possibility of using the single-chain Ab fragment-mediated targeting concept of complement regulatory proteins to restrict complement inhibition to the site of its excessive activation. 相似文献
158.
159.
Casein kinase 1alpha interacts with retinoid X receptor and interferes with agonist-induced apoptosis 总被引:3,自引:0,他引:3
Zhao Y Qin S Atangan LI Molina Y Okawa Y Arpawong HT Ghosn C Xiao JH Vuligonda V Brown G Chandraratna RA 《The Journal of biological chemistry》2004,279(29):30844-30849
Agonists of retinoid X receptors (RXRs), which include the natural 9-cis-retinoic acid and synthetic analogs, are potent inducers of growth arrest and apoptosis in some cancer cells. As such, they are being used in clinical trials for the treatment and prevention of solid tumors and are used to treat cutaneous T cell lymphoma. However, the molecular mechanisms that underlie the anti-cancer effects of RXR agonists remain unclear. Here, we show that a novel pro-apoptotic pathway that is induced by RXR agonist is negatively regulated by casein kinase 1alpha (CK1alpha). CK1alpha associates with RXR in an agonist-dependent manner and phosphorylates RXR. The ability of an RXR agonist to recruit CK1alpha to a complex with RXR in cells correlates inversely with its ability to inhibit growth. Remarkably, depletion of CK1alpha in resistant cells renders them susceptible to RXR agonist-induced growth inhibition and apoptosis. Our study shows that CK1alpha can promote cell survival by interfering with RXR agonist-induced apoptosis. Inhibition of CK1alpha may enhance the anti-cancer effects of RXR agonists. 相似文献
160.
Molina MM Bellí G de la Torre MA Rodríguez-Manzaneque MT Herrero E 《The Journal of biological chemistry》2004,279(50):51923-51930
Glutaredoxins are thiol oxidoreductases that regulate protein redox state. In Saccharomyces cerevisiae, Grx1 and Grx2 are cytosolic dithiol glutaredoxins, whereas Grx3, Grx4, and Grx5 are monothiol glutaredoxins. Grx5 locates at the mitochondrial matrix and is needed for iron/sulfur cluster biogenesis. Its absence causes phenotypes such as inactivation of iron/sulfur enzymes and sensitivity to oxidative stress. Whereas Grx5 contains a single glutaredoxin domain, in Grx3 and Grx4 a thioredoxin-like domain is fused to the glutaredoxin domain. Here we have shown that Grx3 locates at the nucleus and that the thioredoxin-like domain is required for such location. We have addressed the functional divergence among glutaredoxins by targeting Grx2/3/4 molecules to the mitochondrial matrix using the Grx5 targeting sequence. The mitochondrial forms of Grx3 and Grx4 partially rescue the defects of a grx5 null mutant. On the contrary, mitochondrially targeted Grx2 does not suppress the mutant phenotype. Both the thioredoxin-like and glutaredoxin domains are needed for the mitochondrial activity of Grx3, although none of the cysteine residues at the thioredoxin-like domain is required for rescue of the grx5 phenotypes. We have concluded that dithiol glutaredoxins are functionally divergent from monothiol ones, but the latter can interchange their biological activities when compartment barriers are surpassed. 相似文献