全文获取类型
收费全文 | 1253篇 |
免费 | 78篇 |
国内免费 | 1篇 |
专业分类
1332篇 |
出版年
2022年 | 3篇 |
2021年 | 9篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 18篇 |
2015年 | 33篇 |
2014年 | 35篇 |
2013年 | 44篇 |
2012年 | 78篇 |
2011年 | 75篇 |
2010年 | 51篇 |
2009年 | 56篇 |
2008年 | 66篇 |
2007年 | 93篇 |
2006年 | 80篇 |
2005年 | 84篇 |
2004年 | 67篇 |
2003年 | 63篇 |
2002年 | 94篇 |
2001年 | 20篇 |
2000年 | 14篇 |
1999年 | 17篇 |
1998年 | 19篇 |
1997年 | 19篇 |
1996年 | 16篇 |
1995年 | 24篇 |
1994年 | 15篇 |
1993年 | 16篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 11篇 |
1981年 | 18篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 11篇 |
1977年 | 3篇 |
1976年 | 10篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1973年 | 8篇 |
1961年 | 4篇 |
排序方式: 共有1332条查询结果,搜索用时 0 毫秒
21.
Ivan Tayarani Jean Chaudiere Jeanne-Marie Lefauconnier Jean-Marie Bourre 《Journal of neurochemistry》1987,48(5):1399-1402
The content of polyunsaturated fatty acids, the activities of superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase, and the concentration of reduced glutathione were measured in cerebral microvessels isolated from rat brain. Polyunsaturated fatty acids, mainly arachidonic, linoleic, and docosahexaenoic acids, accounted for 32% of total fatty acids in cerebral microvessels. Whereas total SOD activity in the microvessels was slightly lower than that found in cerebrum and cerebellum, glutathione peroxidase and glutathione reductase activities were twice as high and catalase activity was four times higher. Glutathione peroxidase in microvessels is active on both hydrogen peroxide and cumen hydroperoxide, and it is strongly inhibited by mercaptosuccinate. After several hours of preparation, the concentration of reduced glutathione in isolated microvessels was 0.7 mumol/mg of protein, which corresponds to a concentration of approximately 3.5 mM. Our results indicate that the blood-brain barrier contains large amounts of peroxide-detoxifying enzymes, which may act, in vivo, to protect its highly polyunsaturated membranes against oxidative alterations. 相似文献
22.
Dominique Toussaint-Demylle Jean-Marie Scheiff Stanislas Haumont 《Cell and tissue research》1990,262(1):115-123
Summary Thymic nurse cells (TNC), which are multicellular complexes composed of epithelial cells and thymocytes, were obtained from C3H-mice thymuses. They were described by means of light and electron microscopy. The morphology of epithelial cells forming isolated TNC compared to that of small tissue fragments obtained by enzymatic digestion revealed that TNC could be derived from all parts of the thymus: cortex, corticomedullary junction and medulla, the cortex being their principal source. This variety of origin, the presence of several epithelial cells inside a single TNC, the presence of non-lymphoid cells, and the various locations of eleaved desmosomes confirmed that their aspect in vitro as round and sealed structures can be considered to be an artifact due to the isolation technique used. Indeed, during this procedure, they are formed by a process of wrapping of the epithelial cytoplasm around the tightly associated thymocytes. All three epithelial cell types: cortical reticular cells, medullary reticular cells, and medullary globular cells can form TNC.A portion of this work was presented at the first Thymus Workshop. Rolduc, Netherlands, April, 1988 相似文献
23.
Marwen Moussa Vincent Espinasse Jean-Marie Perrier-Cornet Patrick Gervais 《Applied microbiology and biotechnology》2009,85(1):165-174
We investigated the influence of cell hydration on the ability of Saccharomyces cerevisiae CBS 1171 to withstand extreme hydrostatic pressure in order to determine the mechanisms involved in cell resistance. Hydration
conditions were modified in two different ways. We first modulated the chemical potential of water by adding glycerol in cell
suspensions. Another procedure consisted in dehydrating cells aerobically and immersing them in perfluorooctane, an innocuous
hydrophobic liquid used as a pressure-transmitting medium, prior to pressure treatments. This original method made it possible
to transmit isostatic pressure to yeast powders without changing the initial water activity (a
w) level at which cells had been equilibrated. The a
w ranged between 0.11 and 0.99. Pressure treatments were applied at levels of up to 600 MPa for 10 min, 24 h, and 6 days. The
dehydration of cells was found to strongly limit, or even prevent, cell inactivation under pressure. Notably, cells suspended
in a water–glycerol mixture with a
w levels of 0.71 or below were completely protected against all pressure treatments. Moreover, cells dehydrated aerobically
survived for 6 days at 600 MPa even when a
w levels were relatively high (up to 0.94). We highlighted the crucial role of water content in determining cellular damage
under pressure. When water is available in a sufficient amount, high pressure induces membrane permeabilization, causing uncontrolled
mass transfers that could lead to death during a prolonged holding under pressure. Possible mechanisms of membrane permeabilization
are discussed. 相似文献
24.
Anne Mouré Elodie Bacou Steffi Bosch Dominique Jegou Apolline Salama David Riochet Olivier Gauthier Gilles Blancho Jean-Paul Soulillou Denis Poncelet Eric Olmos Jean-Marie Bach Mathilde Mosser 《Biotechnology and bioengineering》2019,116(5):1176-1189
The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O2 supply after transplantation remains a major challenge. In this study, we address the O2 limitation by combining silicone-encapsulated CaO2 (silicone-CaO2) to generate O2 with an extracellular hemoglobin O2-carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O2-diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O2 species produced by silicone-CaO2. While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO2 alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO2 alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O2 provider with hemoglobin as an effective strategy to overcome O2 limitations in tissue engineering. 相似文献
25.
Isabelle Cloëz Ivan Tayarani Frédérique Morel Jean-Marie Bourre 《Journal of neurochemistry》1989,52(5):1353-1358
The activities of peroxide-detoxifying enzymes such as superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalase were measured in the nervous system of neurological dysmyelinating mutants: quaking (Qk), shiverer (Shi), and trembler (Tr) mice. Cu/Zn-SOD activity was higher in the cerebellum of Qk and Shi mice (by 53% and 106%, respectively) in comparison with controls, but it was the same in the cerebellum of Tr mice and their corresponding controls. In contrast, there was no difference in the level of Cu/Zn-SOD activity in the cerebrum of Qk, Shi, and Tr mice and their respective controls. Mn-SOD activity was the same among all the mutants compared to control animals in both cerebrum and cerebellum. In Shi cerebellum, glutathione peroxidase and glutathione reductase activities were slightly decreased (a 21.6% and a 13.2% diminution, respectively), whereas catalase activity in cerebrum and cerebellum was the same among mutants and control mice. In the sciatic nerve from Tr mice, all the enzymatic activities were enhanced: sixfold increase for total SOD, and 2.4-fold, 3.5-fold, and 1.8-fold increase for glutathione peroxidase, glutathione reductase, and catalase, respectively. 相似文献
26.
Lucie Khemtémourian Sébastien Lavielle Katell Bathany Jean-Marie Schmitter Erick J Dufourc 《Journal of peptide science》2006,12(5):361-368
Solid-phase syntheses of the hydrophobic peptides Neu(TM35) ((1)EQRASPVTFIIATVVGVLLFLILVVVVGILIKRRR(35)) and Neu*(TM35) ((1)EQRASPVTFIIATVEGVLLFLILVVVVGILIKRRR(35)), corresponding to the native and mutated (V15E) transmembrane domain of the neu/erbB-2 tyrosine kinase receptor, respectively, were accomplished using Fmoc chemistry. The use of a new resin and cleavage and purification conditions led to large increases in yields and peptide purity. Two (15)N-labelled versions of both wild type and mutated peptides were also synthesized. Approximately 20-40 mg of peptide was obtained using a small-scale synthesis, whereas ca 100 mg of pure peptide was collected on a medium scale. Peptide purity, as monitored by HPLC and mass spectrometry, ranged from 95 to 98% for the six peptides synthesized. Secondary structure as determined by UV circular dichroism (CD) in trifluoroethanol (TFE) showed ca 74% alpha-helical content for the native peptide and ca 63% for that bearing the mutation. Secondary structure of Neu(TM35) was retained in DMPC (dimyristoylphosphatidylcholine)/DCPC (dicaproylphosphatidylcholine) membrane bicelles, and evidences for dimers/oligomers in the lipid bilayer were found. 相似文献
27.
Anthony Laugeray Jean-Marie Launay Jacques Callebert Oguz Mutlu Gilles J. Guillemin Catherine Belzung Pascal R. Barone 《PloS one》2016,11(11)
We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure—a validated model of stress-induced depression—results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine. More importantly we demonstrated that 1-methyl-D-tryptophan was able to alleviate most of the behavioural changes resulting from UCMS exposure. We also showed that both fluoxetine and 1-methyl-D-tryptophan robustly reduced peripheral levels of proinflammatory cytokines in UCMS mice suggesting that their therapeutic effects might occur through anti-inflammatory processes. KP inhibition might be involved in the positive effects of fluoxetine on mice behaviour and could be a relevant strategy to counteract depressive-like symptoms. 相似文献
28.
Øystein Rist Marie Grimstrup Jean-Marie Receveur Thomas M. Frimurer Trond Ulven Evi Kostenis Thomas Högberg 《Bioorganic & medicinal chemistry letters》2010,20(3):1177-1180
Structure–activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP). 相似文献
29.
Eugene Diatloff Rémi Peyronnet Jean Colcombet Sébastien Thomine Hélène Barbier-Brygoo Jean-Marie Frachisse 《Plant signaling & behavior》2010,5(11):1347-1352
Plant genomes code for channels involved in the transport of cations, anions and uncharged molecules through membranes. Although the molecular identity of channels for cations and uncharged molecules has progressed rapidly in the recent years, the molecular identity of anion channels has lagged behind. Electrophysiological studies have identified S-type (slow) and R-type (rapid) anion channels. In this brief review, we summarize the proposed functions of the R-type anion channels which, like the S-type, were first characterized by electrophysiology over 20 years ago, but unlike the S-type, have still yet to be cloned. We show that the R-type channel can play multiple roles.Key words: R-type anion channel, nitrate, sulphate, guard cell, action potentialAnion channels play a central role in signal transduction, nutrient transport and cell turgor regulation.1 By far, their function was particularly well investigated in the guard cells of stomata using a combination of electrophysiological, pharmacological and genetic tools. In this system, anion channel activation was shown to be one of the limiting steps in the loss of cell turgor leading to stomatal closure.2 In algal cells, anion channels were shown to contribute to membrane excitability through the generation of action potential.1,3With the burst of molecular biology in the nineties, the genes coding for plant ion channels started to be unveiled. The first channel gene to be cloned in plant was the shaker-like potassium channel identified in a yeast functional expression screen.4,5 More than ten years later, TaALMT1 and AtCLCa were characterized as the first members of two important anion channel families.6,7 This growing group of newly identified channels, accounting for electrophysiological activity described long ago, includes the MSLs anion selective mechanosensitive channels.8 Recently, the well known S-type channel has been finally recognized to be encoded by members of the SLAC1 (and other SLAH) family (Slow Anion Channel-Associated 1).9 In agreement with electrophysiological data,10–13 it requires phosphorylation by a Protein Kinase in order to be functional.14,15 In contrast, the molecular identity of the R-type anion channel remains unknown. Therefore, this candidate, which has been functionally known since twenty years, remains the next challenge for plant channel physiologists. 相似文献
30.
Monique Berthelon Catherine Caillaud Françoise Rey Philippe Labrune Dominique Melle Josué Feingold Jean Frézal Marie-Louise Briard Jean-Pierre Farriaux Pierre Guibaud Hubert Journel Bernard Le Marec Nicole Maurin Jean-Louis Nivelon Henri Plauchu Jean-Marie Saudubray Philippe Tron Jean Rey Arnold Münnich Stanislas Lyonnet 《Human genetics》1991,86(4):355-358
Summary A total of 252 chromosomes from 126 patients with phenylalanine hydroxylase (PAH) deficiencies were analyzed for both mutant genotypes and restriction fragment length polymorphism (RFLP) haplotypes at the PAH locus. The mutant genes studied originated either from Western Europe (116 alleles) or from Mediterranean countries (136 alleles). Only 27% of all mutant alleles were found to carry identified mutations, particularly mutations at codon 252 (2.3%), 261 (7.5%), 280 (6.3%), 408 (3.5%) and at the splice donor site of intron 12 (6.3%). The mutant genotypes were associated with RFLP haplotypes 7, 1, 38, 2 and 3 at the PAH locus respectively. Except for the splice mutation of intron 12, these associations were preferential, but not exclusive, since the other four mutations were found on the background of at least two RFLP haplotypes. These results, together with the observation that 85% of PAH deficient patients are heterozygotes for their mutant genotypes, emphasize the great heterogeneity of PAH deficiencies in Mediterranean countries and hamper systematic DNA testing for carrier status in this population. 相似文献