全文获取类型
收费全文 | 2136篇 |
免费 | 208篇 |
国内免费 | 2篇 |
出版年
2023年 | 9篇 |
2022年 | 5篇 |
2021年 | 36篇 |
2020年 | 28篇 |
2019年 | 21篇 |
2018年 | 30篇 |
2017年 | 25篇 |
2016年 | 48篇 |
2015年 | 86篇 |
2014年 | 103篇 |
2013年 | 133篇 |
2012年 | 181篇 |
2011年 | 167篇 |
2010年 | 100篇 |
2009年 | 119篇 |
2008年 | 143篇 |
2007年 | 157篇 |
2006年 | 114篇 |
2005年 | 119篇 |
2004年 | 117篇 |
2003年 | 104篇 |
2002年 | 93篇 |
2001年 | 34篇 |
2000年 | 30篇 |
1999年 | 32篇 |
1998年 | 33篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 17篇 |
1994年 | 16篇 |
1993年 | 20篇 |
1992年 | 19篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 11篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 6篇 |
1971年 | 6篇 |
1969年 | 10篇 |
1967年 | 9篇 |
排序方式: 共有2346条查询结果,搜索用时 15 毫秒
991.
Thomas Brillet Véronique Baudin-Creuza Corinne Vasseur Elisa Domingues-Hamdi Laurent Kiger Henri Wajcman Serge Pissard Michael C. Marden 《The Journal of biological chemistry》2010,285(23):17986-17992
A kinetic analysis has been made of the interaction of α-Hb chains with a mutant α-hemoglobin stabilizing protein, AHSPV56G, which is the first case of an AHSP mutation associated with clinical symptoms of mild thalassemia syndrome. The chaperone AHSP is thought to protect nascent α chains until final binding to the partner β-Hb. Rather than protecting α chains, the mutant chaperone is partially unfolded but recovers its secondary structure via interaction with α-Hb. For both AHSPWT and AHSPV56G, the binding to α-Hb is quite rapid relative to the α-β reaction, as expected because the chaperone binding must be quite competitive to complete the α chain folding process before α-Hb binds irreversibly to β-Hb. The main kinetic difference is a dissociation rate of AHSPV56G·α-Hb some four times faster relative to AHSP·α-Hb. Considering a role of protein folding, the AHSPV56G apparently does not bind long enough (0.5 s versus 2 s for the WT) to complete the structural modifications. The overall replacement reaction (AHSP·α-Hb + β-Hb → AHSP + αβ) can be quite long, especially if there is an excess of AHSP relative to β-Hb monomers. 相似文献
992.
Agnieszka Robaszkiewicz Fiona H. Greig Andrew R. Pitt Corinne M. Spickett Grzegorz Bartosz Mirosław Soszyński 《Chemistry and physics of lipids》2010,163(7):639-647
Hypochlorite generated in vivo under pathological conditions is a known oxidant and chlorinating agent, able to react with proteins and lipids, which affects the stability of biological membranes. Reaction with unsaturated fatty acyl chains in glycerophospholipids such as phosphatidylcholine results in the formation of chlorohydrins. The aim of this study was to determine the effects of chlorohydrins formed by the reaction of hypochlorite with 1-stearoyl-2-oleoyl-, 1-stearoyl-2-linoleoyl-, and 1-stearoyl-2-arachidonylphosphatidylcholine on biophysical properties of bilayers and their effects on human erythrocytes. Using electrospray mass spectrometry we observed complete conversion of the lipids into chlorohydrins, which resulted in a decrease in the rotational correlation time and an increase in the order parameter of liposomes. Unilamellar chlorohydrin liposomes had a lower permeation coefficient for calcein than liposomes made of parent lipids. Flow cytometry demonstrated fast incorporation of uni and multilamellar chlorohydrin liposomes labeled with NBD-phosphatidylethanolamine into erythrocytes. This effect was accompanied by changes in erythrocyte shape (echinocyte formation) and aggregation. Similar but less pronounced effects were noticed for parent lipids only after longer incubation. Chlorohydrins showed also a stronger hemolytic action, proportional to the lipid:erythrocyte ratio. These results are important for understanding the effects of HOCl on mammalian cells, such as might occur in inflammatory pathology. 相似文献
993.
994.
Graziello Geneau Coralie Lamiche Corinne Niger Pierre-Olivier Strale Jonathan Clarhaut Norah Defamie Françoise Debiais Marc Mesnil Laurent Cronier 《Cell and tissue research》2010,340(1):103-115
Bone is a dynamic tissue that undergoes a precise remodeling process involving resorptive osteoclastic cells and bone-forming
osteoblastic (OB) cells. The functional imbalance of either of these cell types can lead to severe skeletal diseases. The
proliferation and differentiation of OB cells play a major role in bone development and turnover. These cellular processes
are coordinated by connexin43 (Cx43)-based gap-junctional intercellular communication (GJIC) and by soluble factors such as
endothelin-1 (ET-1). We have used the Cx43 heterozygous (Cx43+/−) murine model to study the possible cross-talk between Cx43 and ET-1 in cultured calvarial OB cells. On microcomputed tomographic
analysis of 3-day-old pups, Cx43+/− mice showed hypomineralized calvaria in comparison with their Cx43+/+ littermates. Characterization of cultured OB cells clearly demonstrated the effect of the partial deletion of the Cx43 gene
on its expression, on GJIC, and subsequently on OB differentiation. In this model, ET-1 (10−8 M) lost its mitogenic action in Cx43+/− OB cells compared with Cx43+/+ cells. Moreover, a correlation between the inhibition of cell differentiation by ET-1 and the decreased amount and function
of Cx43 was found in Cx43+/+ OB cells but not in their Cx43+/− counterparts. Thus, as Cx43 is linked to OB differentiation, our data indicate that this mitogenic ET-1 peptide has pronounced
effects on fully differentiated OB cells. With respect to roles in mechanotransduction and OB differentiation, Cx43 might
modulate osteoblastic sensitivity to soluble factors. 相似文献
995.
Corinne Zurbrügg Linda Hönemann Michael Meissle Jörg Romeis Wolfgang Nentwig 《Transgenic research》2010,19(2):257-267
The cultivation of genetically modified Bt maize has raised environmental concerns, as large amounts of plant residues remain in the field and may negatively impact
the soil ecosystem. In a field experiment, decomposition of leaf residues from three genetically modified (two expressing
the Cry1Ab, one the Cry3Bb1 protein) and six non-transgenic hybrids (the three corresponding non-transformed near-isolines
and three conventional hybrids) was investigated using litterbags. To elucidate the mechanisms that cause differences in plant
decomposition, structural plant components (i.e., C:N ratio, lignin, cellulose, hemicellulose) were examined. Furthermore,
Cry1Ab and Cry3Bb1 protein concentrations in maize leaf residues were measured from harvest to the next growing season. While
leaf residue decomposition in transgenic and non-transgenic plants was similar, differences among conventional cultivars were
evident. Similarly, plant components among conventional hybrids differed more than between transgenic and non-transgenic hybrids.
Moreover, differences in senescent plant material collected directly from plants were larger than after exposure to soil for
5 months. While the concentration of Cry3Bb1 was higher in senescent maize leaves than that of Cry1Ab, degradation was faster,
indicating that Cry3Bb1 has a shorter persistence in plant residues. As decomposition patterns of Bt-transgenic maize were shown to be well within the range of common conventional hybrids, there is no indication of ecologically
relevant, adverse effects on the activity of the decomposer community. 相似文献
996.
Hydrobiologia - Changing reproductive strategy from investment in current (asexual eggs) to future (sexual ephippia) reproduction depending on environmental cues is an important fitness trait in... 相似文献
997.
RASSF4, a member of the classical RASSF family of scaffold proteins, is associated with alveolar rhabdomyosarcoma, an aggressive pediatric cancer of muscle histogenesis. However, the role of RASSF4 in normal myogenesis is unknown. We demonstrate here that RASSF4 is necessary for early in vitro myogenesis. Using primary human myoblasts, we show that RASSF4 expression is dramatically increased during in vitro myogenic differentiation, and conversely that RASSF4‐deficient myoblasts cannot differentiate, potentially because of a lack of upregulation of myogenin. In microscopy studies, we show that RASSF4 protein co‐localizes with proteins of the myogenic microtubule‐organizing center (MTOC) both before and after myogenic differentiation. RASSF4‐deficient cells subject to differentiation conditions demonstrate a lack of shape change, suggesting that RASSF4 plays a role in promoting microtubule reorganization and myoblast elongation. In biochemical studies of myotubes, RASSF4 associates with MST1, suggesting that RASSF4 signals to MST1 in the myogenic differentiation process. Expression of MST1 in myoblasts partially reversed the effect of RASSF4 knockdown on differentiation, suggesting that RASSF4 and MST1 coordinately support myogenic differentiation. These data show that RASSF4 is critical for the early steps of myogenic differentiation. 相似文献
998.
Cory J. D. Matthews Rocio I. Ruiz‐Cooley Corinne Pomerleau Steven H. Ferguson 《Ecology and evolution》2020,10(7):3450-3462
Compound‐specific stable isotope analysis (CSIA) of amino acids (AAs) has been rapidly incorporated in ecological studies to resolve consumer trophic position (TP). Differential 15N fractionation of “trophic” AAs, which undergo trophic 15N enrichment, and “source” AAs, which undergo minimal trophic 15N enrichment and serve as a proxy for primary producer δ15N values, allows for internal calibration of TP. Recent studies, however, have shown the difference between source and trophic AA δ15N values in higher marine consumers is less than predicted from empirical studies of invertebrates and fish. To evaluate CSIA‐AA for estimating TP of cetaceans, we compared source and trophic AA δ15N values of multiple tissues (skin, baleen, and dentine collagen) from five species representing a range of TPs: bowhead whales, beluga whales, short‐beaked common dolphins, sperm whales, and fish‐eating (FE) and marine mammal‐eating (MME) killer whale ecotypes. TP estimates (TPCSIA) using several empirically derived equations and trophic discrimination factors (TDFs) were 1–2.5 trophic steps lower than stomach content‐derived estimates (TPSC) for all species. Although TPCSIA estimates using dual TDF equations were in better agreement with TPSC estimates, our data do not support the application of universal or currently available dual TDFs to estimate cetacean TPs. Discrepancies were not simply due to inaccurate TDFs, however, because the difference between consumer glutamic acid/glutamine (Glx) and phenylalanine (Phe) δ15N values (δ15NGlx‐Phe) did not follow expected TP order. In contrast to pioneering studies on invertebrates and fish, our data suggest trophic 15N enrichment of Phe is not negligible and should be examined among the potential mechanisms driving “compressed” and variable δ15NGlx‐Phe values at high TPs. We emphasize the need for controlled diet studies to understand mechanisms driving AA‐specific isotopic fractionation before widespread application of CSIA‐AA in ecological studies of cetaceans and other marine consumers. 相似文献
999.
1000.
Ludivine Hocq Sophie Guinand Olivier Habrylo Aline Voxeur Wafae Tabi Josip Safran Franoise Fournet Jean‐Marc Domon Jean‐Claude Mollet Serge Pilard Corinne Pau‐Roblot Arnaud Lehner Jrme Pelloux Valrie Lefebvre 《The Plant journal : for cell and molecular biology》2020,103(2):617-633
Plant cell wall remodeling plays a key role in the control of cell elongation and differentiation. In particular, fine‐tuning of the degree of methylesterification of pectins was previously reported to control developmental processes as diverse as pollen germination, pollen tube elongation, emergence of primordia or elongation of dark‐grown hypocotyls. However, how pectin degradation can modulate plant development has remained elusive. Here we report the characterization of a polygalacturonase (PG), AtPGLR, the gene for which is highly expressed at the onset of lateral root emergence in Arabidopsis. Due to gene compensation mechanisms, mutant approaches failed to determine the involvement of AtPGLR in plant growth. To overcome this issue, AtPGLR has been expressed heterologously in the yeast Pichia pastoris and biochemically characterized. We showed that AtPGLR is an endo‐PG that preferentially releases non‐methylesterified oligogalacturonides with a short degree of polymerization (< 8) at acidic pH. The application of the purified recombinant protein on Amaryllis pollen tubes, an excellent model for studying cell wall remodeling at acidic pH, induced abnormal pollen tubes or cytoplasmic leakage in the subapical dome of the pollen tube tip, where non‐methylesterified pectin epitopes are detected. Those leaks could either be repaired by new β‐glucan deposits (mostly callose) in the cell wall or promoted dramatic burst of the pollen tube. Our work presents the full biochemical characterization of an Arabidopsis PG and highlights the importance of pectin integrity in pollen tube elongation. 相似文献