全文获取类型
收费全文 | 907篇 |
免费 | 58篇 |
出版年
2021年 | 16篇 |
2020年 | 9篇 |
2019年 | 16篇 |
2018年 | 19篇 |
2017年 | 10篇 |
2016年 | 22篇 |
2015年 | 39篇 |
2014年 | 46篇 |
2013年 | 58篇 |
2012年 | 73篇 |
2011年 | 57篇 |
2010年 | 22篇 |
2009年 | 34篇 |
2008年 | 45篇 |
2007年 | 50篇 |
2006年 | 51篇 |
2005年 | 26篇 |
2004年 | 43篇 |
2003年 | 32篇 |
2002年 | 34篇 |
2001年 | 18篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 14篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 11篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1969年 | 7篇 |
1968年 | 5篇 |
1967年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有965条查询结果,搜索用时 15 毫秒
131.
Sara P. De Martino Fiona Errington Alan Ashworth Trevor Jowett C. A. Austin 《Development genes and evolution》1999,209(6):357-362
The Sox family of proteins is thought to act to regulate gene expression in a wide variety of developmental processes. Here
we describe the cloning of sox30, a novel sox gene from the zebrafish (Danio rerio). In situ hybridization shows that sox30 is expressed in a restricted manner at the boundary between the midbrain and hindbrain during nervous system development.
This expression pattern is in direct contrast to that of most other neuronally expressed Sox genes which are expressed throughout the nervous system.
Received: 30 October 1998 / Accepted: 1 February 1999 相似文献
132.
The membrane potential of cultured bovine aortic endothelial cells was assessed by a fluorescent probe as an alternative to direct methods. We used the fluorescent cationic dye rhodamine 6G, a lipophilic probe with high permeability in cell membranes. A linear relationship was obtained between fluorescence intensity (F.I.) and membrane potential (Em) as a function of the extracellular Na(+) concentration in the presence of the ionophore gramicidin. From the equation derived from the linear relationship F.I. = -0.004 Em + 0. 03 (P < 0.001), the fluorescence measurements could be converted to membrane potential. The resting plasma membrane potential obtained was -65 +/- 7 mV. Nigericin (27 microM), ouabain (1 mM), and bradykinin (20 nM) induced a decrease in F.I. (depolarization), while ATP (25-100 microM) induced an increase in F.I. (hyperpolarization). Mitochondrial membrane potential inhibitors myxothiazol (3 microM) and oligomycin (4 microM) did not influence F. I. measured in the cultured bovine aortic endothelial cells. The results indicate that rhodamine 6G can be used as a sensitive and specific dye in studies of substances that affect the membrane potential of endothelial cells. 相似文献
133.
134.
Clemente Capasso Menico Rizzi Enea Menegatti Paolo Ascenzi Martino Bolognesi 《Journal of molecular recognition : JMR》1997,10(1):26-35
The crystal structure of bovine α-chymotrypsin (α-CHT) in complex with the bovine basic pancreatic trypsin inhibitor (BPTI) has been solved and refined at 2.8 Å resolution (R-factor=0.18). The proteinase:inhibitor complex forms a compact dimer (two α-CHT and two BPTI molecules), which may be stabilized by surface-bound sulphate ions, in the crystalline state. Each BPTI molecule, at opposite ends, is contacting both proteinase molecules in the dimer, through the reactive site loop and through residues next to the inhibitor's C-terminal region. Specific recognition between α-CHT and BPTI occurs at the (re)active site interface according to structural rules inferred from the analysis of homologous serine proteinase:inhibitor complexes. Lys15, the P1 residue of BPTI, however, does not occupy the α-CHT S1 specificity pocket, being hydrogen bonded to backbone atoms of the enzyme surface residues Gly216 and Ser217. © 1997 John Wiley & Sons, Ltd. 相似文献
135.
Andrea Sacconi Claudia De Vitis Luisa de Latouliere Simona di Martino Francesca De Nicola Frauke Goeman Carla Mottini Francesca Paolini Michela DAscanio Alberto Ricci Agostino Tafuri Paolo Marchetti Arianna Di Napoli Luciano De Biase Andrea Negro Christian Napoli Paolo Anibaldi Valentina Salvati Darragh Duffy Benjamin Terrier Maurizio Fanciulli Carlo Capalbo Salvatore Sciacchitano Giovanni Blandino Giulia Piaggio Rita Mancini Gennaro Ciliberto 《Cell death & disease》2021,12(11)
136.
Tattoli I Lembo-Fazio L Nigro G Carneiro LA Ferraro E Rossi G Martino MC de Stefano ME Cecconi F Girardin SE Philpott DJ Bernardini ML 《Microbes and infection / Institut Pasteur》2008,10(10-11):1114-1123
Infected epithelial cells, which act as a first barrier against pathogens, seldom undergo apoptosis. Rather, infected epithelial cells undergo a slow cell death that displays hallmarks of necrosis. Here, we demonstrate that rapid intracellular lysis of Shigella flexneri, provoked by either the use of a diaminopimelic acid auxotroph mutant or treatment of infected cells with antibiotics of the beta-lactam family, resulted in a massive and rapid induction of apoptotic cell death. This intracellular bacteriolysis-mediated apoptotic death (IBAD) was characterized by the specific involvement of the mitochondrial-dependent cytochrome c/Apaf-1 axis that resulted in the activation of caspases-3, -6 and -9. Importantly, Bcl-2 family members and the NF-kappaB pathway seemed to be critical modulators of IBAD. Finally, we identified that IBAD was also triggered by Salmonella enterica serovar Typhimurium but not by the Gram-positive bacteria, Listeria monocytogenes. Together, our results demonstrate that, contrary to previous findings, epithelial cells are intrinsically able to mount an efficient apoptotic cell death response following infection. Indeed, apoptosis in normal circumstances is masked by powerful anti-apoptotic mechanisms, which are overcome in IBAD. Our results also uncover an unexpected consequence of the treatment of infected cells with certain classes of antibiotics. 相似文献
137.
In the last decade the role of structural dynamics in controlling protein function was actively investigated using new and advanced experimental approaches. In particular, time resolved crystallography, despite some practical difficulties, is being used extensively to complement the study of protein structure-function relationships with information on the dynamics, based on experimental evidence. Here we present a short overview of the results obtained on dynamical properties of myoglobin and homologous hemoproteins, where the photosensitive heme-Fe--ligand bond has allowed transient intermediates to be studied by different flash photolysis methods coupled to Laue X-ray diffraction, thus highlighting some of the dynamical events that characterize diffusion of a diatomic ligand to/from the heme in model hemoproteins. 相似文献
138.
Di Gioacchino M Petrarca C Perrone A Martino S Esposito DL Lotti LV Mariani-Costantini R 《Autophagy》2008,4(4):537-539
The inherent toxicity of many metal compounds, together with their widespread environmental distribution, raises concerns of potential health hazards. Little is known about the impact of these important environmental toxicants on adult stem/progenitor cells, necessary for tissue homeostasis and repair. We recently reported that autophagy is implicated in the response of hematopoietic stem/progenitor cells to toxic concentrations of hexavalent chromium (Cr[VI]) and cadmium (Cd), two well known carcinogenic heavy metal cations. Autophagy may lead to cell death if carried out too extensively, but also acts as a survival pathway in cells under stress. In stem/progenitor cells, an autophagic phenotype could mitigate metal-induced toxicity, contributing to the conservation of tissue renewal capability. Given the key role of toxic damage to adult stem/progenitor cells in cancer, it is necessary to investigate whether autophagic responses modulate the carcinogenic potential of exposure to heavy metals during stem/progenitor cell differentiation. 相似文献
139.
Fiorito F Pagnini U De Martino L Montagnaro S Ciarcia R Florio S Pacilio M Fucito A Rossi A Iovane G Giordano A 《Journal of cellular biochemistry》2008,103(1):221-233
Dioxin-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental toxin of current interest. In the last years, higher levels of TCDD than those permitted in UE [European Commission. 2002. European Commission Recommendation 2002/201/CE. Official Gazette, L 67/69] were detected in milk samples from cow, water buffalo, goat, and sheep raised on some areas of Campania Region (South Italy). Dioxin often causes immunosuppression and might render the animal liable to viral infections. In addition, viral infections are able to alter the pattern of dioxin distribution in different organs of the exposed animals. Bovine Herpesvirus type-1 (BHV-1) is a widespread pathogen, which causes infectious rhinotracheitis and infectious pustular vulvovaginitis in cattle. Herein, we have studied the effects of TCDD and BHV-1 infection, in Madin-Darby Bovine Kidney (MDBK) cells, alone as well as in association, so as cellular proliferation, apoptosis, and virus replication. We have observed an increase in cell viability of confluent monolayers at low TCDD concentrations. TCDD treated cells demonstrated increased viability compared to controls as evaluated by MTT test. TCDD exposure increased cell proliferation but induced no changes on apoptosis. Cells exposed to TCDD along with BHV-1 showed a dose-dependent increase in cytopathy, represented by ample syncytia formation with the elimination of the cellular sheets and increased viral titer. These results suggest that TCDD increases viral replication in MDBK cells while BHV-1 further decreases viability of TCDD exposed cells. Since very low concentrations (0.01 pg/ml) are sufficient to augment BHV-1 titer, TCDD may contribute to reactivate BHV-1 from latency, leading to recurrent disease and increase virus transmission. 相似文献
140.
Maffettone C De Martino L Irace C Santamaria R Pagnini U Iovane G Colonna A 《Journal of cellular biochemistry》2008,104(1):213-223
Bovine herpesvirus 1 (BHV-1), a dsDNA animal virus, is an economically important pathogen of cattle and the aetiological agent of many types of disease. The efficient replication of a DNA virus is strictly dependent on iron since this metal plays a crucial role in the catalytic center of viral ribonucleotide reductase. Consequently, iron metabolism is an important area for virus/host interaction and a large body of evidence suggests that viral infection is potentially influenced by the iron status of the host. The aim of the present study was to address the effects of BHV-1 on iron metabolism in Madin-Darby bovine kidney (MDBK) cells at different times of post-infection. For this purpose, cell viability, iron regulatory proteins (IRPs) activity and levels, transferrin receptor 1 (TfR-1), ferritin expression and LIP were evaluated. Our data demonstrate that a productive BHV-1 infection in MDBK cells determines an overall decrease of IRPs RNA-binding activity without affecting their expression. As consequence of this modulation, an increased ferritin mRNA translation and a decreased TfR-1 mRNA translation were also observed. Moreover, the LIP level was decreased following viral infection. These results are consistent with the hypothesis that by reducing the iron up-take and by enhancing the sequestration of free iron, animal cells will limit the iron availability for virus proliferation. Therefore, the results presented herein support the view that iron metabolism could be critical for the interaction between DNA viruses, such as BHV-1, and mammalian cells. Delineation of the interplay among pathogen and host may provide new antimicrobial agents. 相似文献