全文获取类型
收费全文 | 1876篇 |
免费 | 124篇 |
出版年
2024年 | 3篇 |
2023年 | 13篇 |
2022年 | 28篇 |
2021年 | 74篇 |
2020年 | 35篇 |
2019年 | 47篇 |
2018年 | 58篇 |
2017年 | 41篇 |
2016年 | 67篇 |
2015年 | 111篇 |
2014年 | 102篇 |
2013年 | 152篇 |
2012年 | 190篇 |
2011年 | 207篇 |
2010年 | 107篇 |
2009年 | 99篇 |
2008年 | 120篇 |
2007年 | 93篇 |
2006年 | 92篇 |
2005年 | 83篇 |
2004年 | 83篇 |
2003年 | 61篇 |
2002年 | 51篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1968年 | 8篇 |
1964年 | 1篇 |
排序方式: 共有2000条查询结果,搜索用时 15 毫秒
941.
C. Betti C. Lico M. Iriti S. D’Angeli E. Benvenuto S. Baschieri 《Plant biosystems》2013,147(3):725-732
Abstract The cytopathology of a Potato virus X (PVX) recombinant variant (encoding as fusion of an epitope of immunological interest with the N‐terminus of the coat protein, PVXSmaP18DD) has been compared with that induced by the wild‐type virus (PVX wt) in Nicotiana benthamiana plants. Both PVX wt and PVXSmaP18DD caused similar ultrastructural alterations, characterized by the presence of laminated inclusion components and bulk virus accumulations in mesophyll cells. However, some striking differences were observed not only in the morphology of these accumulations (typically ordered in PVX wt infection and disordered in PVXSmaP18DD infection) but also because the chimeric virus caused peculiar alterations in chloroplasts structure. Abbreviations: CP, coat protein; d.p.i., days post inoculation; LIC, laminated inclusion components; PVX, Potato virus X 相似文献
942.
The protective activity of hypotaurine (HTAU) and cysteine sulphinic acid (CSA) on peroxynitrite-mediated oxidative damage has been assessed by monitoring different target molecules, i.e. tyrosine, dihydrorhodamine-123 (DHR) and glutathione (GSH). The inhibition of tyrosine oxidation exerted by HTAU and CSA both in the presence and the absence of bicarbonate can be ascribed to their ability to scavenge hydroxyl (?OH) and carbonate (CO3??) radicals. HTAU and CSA also reduce tyrosyl radicals, suggesting that this repair function of sulphinates might operate as an additional inhibiting mechanism of tyrosine oxidation. In the peroxynitrite-dependent oxidation of DHR, the inhibitory effect of HTAU was lower than that of CSA. Moreover, while HTAU and CSA competitively inhibited the direct oxidation of GSH by peroxynitrite, HTAU was again poorly effective against the oxidation of GSH mediated by peroxynitrite-derived radicals. The possible involvement of secondary reactions, which could explain the difference in antioxidant activity of HTAU and CSA, is discussed. 相似文献
943.
Yu-Hung Chen Barnabas Szakal Federica Castellucci Dana Branzei Xiaolan Zhao 《Molecular biology of the cell》2013,24(15):2431-2441
DNA damage checkpoint and recombinational repair are both important for cell survival of replication stress. Because these two processes influence each other, isolation of their respective contributions is challenging. Research in budding yeast shows that removal of the DNA helicase Mph1 improves survival of cells with defective Smc5/6 complex under replication stress. mph1∆ is known to reduce the levels of recombination intermediates in smc6 mutants. Here, we show that mph1∆ also hyperactivates the Mec1 checkpoint. We dissect the effects of recombination regulation and checkpoint hyperactivation by altering the checkpoint circuitry to enhance checkpoint signaling without reducing recombination intermediate levels. We show that these approaches, similar to mph1∆, lead to better survival of smc6 cells upon transient replication stress, likely by ameliorating replication and chromosomal segregation defects. Unlike mph1∆, however, they do not suppress smc6 sensitivity to chronic stress. Conversely, reducing the checkpoint response does not impair survival of smc6 mph1∆ mutants under chronic stress. These results suggest a two-phase model in which smc6 mutant survival upon transient replication stress can be improved by enhancing Mec1 checkpoint signaling, whereas smc6 sensitivity to chronic stress can be overcome by reducing recombination intermediates. 相似文献
944.
Ascenzi P Ciaccio C Sinibaldi F Santucci R Coletta M 《Biochemical and biophysical research communications》2011,(3):463-467
Carboxymethylation of equine heart cytochrome c (cytc) changes its tertiary structure by disrupting the heme-Fe-Met80 distal bond, such that carboxymethylated cytc (CM-cytc) displays myoglobin-like properties. Here, the effect of cardiolipin (CL) on peroxynitrite isomerization by ferric CM-cytc (CM-cytc-Fe(III)) is reported. Unlike native ferric cytc (cytc-Fe(III)), CM-cytc-Fe(III) catalyzes peroxynitrite isomerization, the value of the second order rate constant (kon) is 6.8 × 104 M−1 s−1. However, CM-cytc-Fe(III) is less effective in peroxynitrite isomerization than CL-bound cytc-Fe(III) (CL-cytc-Fe(III); kon = 3.2 × 105 M−1 s−1). Moreover, CL binding to CM-cytc-Fe(III) facilitates peroxynitrite isomerization (kon = 5.3 × 105 M−1 s−1). Furthermore, the value of the dissociation equilibrium constant for CL binding to CM-cytc-Fe(III) (K = 1.8 × 10−5 M) is lower than that reported for CL-cytc-Fe(III) complex formation (K = 5.1 × 10−5 M). Although CM-cytc-Fe(III) and CL-cytc-Fe(III) display a different heme distal geometry and heme-Fe(III) reactivity, the heme pocket and the CL cleft are allosterically linked. 相似文献
945.
Zulian A Sileikytė J Petronilli V Bova S Dabbeni-Sala F Cargnelli G Rennison D Brimble MA Hopkins B Bernardi P Ricchelli F 《Biochimica et biophysica acta》2011,1807(12):1600-1605
We have investigated the mechanism of rat-selective induction of the mitochondrial permeability transition (PT) by norbormide (NRB). We show that the inducing effect of NRB on the PT (i) is inhibited by the selective ligands of the 18kDa outer membrane (OMM) translocator protein (TSPO, formerly peripheral benzodiazepine receptor) protoporphyrin IX, N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide and 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one; and (ii) is lost in digitonin mitoplasts, which lack an intact OMM. In mitoplasts the PT can still be induced by the NRB cationic derivative OL14, which contrary to NRB is also effective in intact mitochondria from mouse and guinea pig. We conclude that selective NRB transport into rat mitochondria occurs via TSPO in the OMM, which allows its translocation to PT-regulating sites in the inner membrane. Thus, species-specificity of NRB toward the rat PT depends on subtle differences in the structure of TSPO or of TSPO-associated proteins affecting its substrate specificity. 相似文献
946.
947.
948.
Sambucci M Laudisi F Nasta F Pinto R Lodato R Lopresto V Altavista P Marino C Pioli C 《Progress in biophysics and molecular biology》2011,107(3):393-398
The development of the immune system begins during embryogenesis, continues throughout fetal life, and completes its maturation during infancy. Exposure to immune-toxic compounds at levels producing limited/transient effects in adults, results in long-lasting or permanent immune deficits when it occurs during perinatal life. Potentially harmful radiofrequency (RF) exposure has been investigated mainly in adult animals or with cells from adult subjects, with most of the studies showing no effects. Is the developing immune system more susceptible to the effects of RF exposure? To address this question, newborn mice were exposed to WiFi signals at constant specific absorption rates (SAR) of 0.08 or 4 W/kg, 2 h/day, 5 days/week, for 5 consecutive weeks, starting the day after birth. The experiments were performed with a blind procedure using sham-exposed groups as controls. No differences in body weight and development among the groups were found in mice of both sexes. For the immunological analyses, results on female and male newborn mice exposed during early post-natal life did not show any effects on all the investigated parameters with one exception: a reduced IFN-γ production in spleen cells from microwaves (MW)-exposed (SAR 4 W/kg) male (not in female) mice compared with sham-exposed mice. Altogether our findings do not support the hypothesis that early post-natal life exposure to WiFi signals induces detrimental effects on the developing immune system. 相似文献
949.
Tessari F Bortolami S Zoccarato F Alexandre A Cavallini L 《Journal of bioenergetics and biomembranes》2011,43(3):267-274
Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H2O2 release at Complex-I. mM SNP increases while GSNO decreases the release induced by succinate alone or added on top of NAD-linked
substrates. Stimulation likely depends on Nitric Oxide (
.
NO) (released by SNP but not by GSNO) inhibiting cytochrome oxidase and mitochondrial respiration. Preincubations with SNP
or high GSNO (10 mM plus DTE to increases its
.
NO release) induces an inhibition of the succinate dependent H2O2 production consistent with a
.
NO dependent covalent modification. However maximal inhibition of the succinate dependent H2O2 release is obtained in the presence of low GSNO (20–100 μM), but not with SNP. This inhibition appears independent of
.
NO release since μM GSNO does not affect mitochondrial respiration, or the H2O2 detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O2.− since GSNO chemically competes with NBT and cytochrome C in O2.− detection. 相似文献
950.
Imberti B Casiraghi F Cugini D Azzollini N Cassis P Todeschini M Solini S Sebastiano V Zuccotti M Garagna S Redi CA Noris M Morigi M Remuzzi G 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(7):4164-4174
Tolerance induction toward allogeneic organ grafts represents one of the major aims of transplantation medicine. Stem cells are promising candidates for promoting donor-specific tolerance. In this study, we investigated the immunomodulatory properties of murine embryonic stem cells (ESCs), obtained either by in vitro fertilization (IVF-ESCs) or by nuclear transfer (NT-ESCs), in heart transplant mouse models. IVF-ESCs did not prolong the survival of fully allogeneic cardiac transplants but significantly prolonged the survival of semiallogeneic hearts from the same ESC donor strain for >100 d in 44% of the animals. However, 28% of transplanted animals infused with IVF-ESCs experienced development of a teratoma. NT-ESCs similarly prolonged semiallogeneic heart graft survival (>100 d in 40% of the animals) but were less teratogenic. By in vitro studies, IVF-ESC and NT-ESC immunoregulation was mediated both by cell contact-dependent mechanisms and by the release of soluble factors. By adding specific inhibitors, we identified PGE(2) as a soluble mediator of ESC immunoregulation. Expansion of regulatory T cells was found in lymphoid organs and in the grafts of IVF-ESC- and NT-ESC-tolerized mice. Our study demonstrates that both IVF-ESCs and NT-ESCs modulate recipient immune response toward tolerance to solid organ transplantation, and that NT-ESCs exhibit a lower tendency for teratoma formation. Because NT-ESCs are obtained by NT of a somatic cell from living individuals into an enucleated oocyte, they could represent a source of donor-derived stem cells to induce tolerance to solid organ allograft. 相似文献