全文获取类型
收费全文 | 254篇 |
免费 | 20篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 15篇 |
2014年 | 10篇 |
2013年 | 22篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 18篇 |
2009年 | 21篇 |
2008年 | 13篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 8篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 11篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有274条查询结果,搜索用时 31 毫秒
1.
Summary Ca2+-activated K+ channels were studied in cultured medullary thick ascending limb (MTAL) cells using the patch-clamp technique in the inside-out configuration. The Ca2+ activation site was modified using N-bromoacetamide (NBA). 1mm NBA in the bath solution, at 2.5 m Ca2+ reduces the open probability,P
o
, of the channel to <0.01, without an effect on single-channel conductance. NBA-modified channels are still Ca2+-sensitive, requiring 25mm Ca2+ to raiseP
o
to 0.2. Both before and after NBA modification channel openings display at least two distributions, indicative of more than one open state. High Ca2+ (1mm) protects the channels from modification. Also presented is a second class of Ca2+-activated K+ channels which are normally present in MTAL cells which open infrequently at 10 m Ca2+ (P
o
=0.01) but have aP
o
of 0.08 at 1mm Ca2+. We can conclude (i) that NBA modifies the channel by shifting Ca2+-sensitivity to very high Ca2+, (ii) that NBA acts on a site involved in Ca2+ gating, and (iii) that a low affinity channel is present in the apical cell membrane with characteristics similar to those of normal channels modified with NBA. 相似文献
2.
The effect of seed aggregation and distance from conspecific trees on seed predation was experimentally examined for two neotropical tree species, Macoubea guianensis (Apocynaceae) and Pouteria sp. (Sapotaceae) in a lowland tropical rain forest in northeastern Peru. Results of these experiments are discussed in the context of the Janzen-Connell model (Janzen 1970; Connell 1971), which predicts decreased seed survival near parent trees due to either density-or distance-responsive mortality, and Howe's model (Howe 1989) which predicts that trees with seeds dispersed in clumps (aggregated) will not suffer density-dependent predation, and will have higher survival of seeds near the parent tree than other trees. We also examined whether predation on seeds of these species was affected by seed placement in or near 30-m-wide strips regenerating after clear-cutting. Both species appeared to be mammal-dispersed but differed in how frugivores handled seeds, seed size, overall fruit crop size, and gemination time. Neither of the two species studied appeared to suffer seed predation in a manner predicted by the Janzen-Connell model, and patterns of seed predation for only one of the species was similar to predictions of Howe's model. For neither species did seed predation along the edge of, or in the center of, regenerating clear cuts differ from predation 15 m into the primary forest. For Pouteria, seed predation in and near regnerating strips was significantly greater than around forest trees, but the opposite pattern held for Macoubea. Overall, seed predation was much greater on Macoubea. The difference in seed predation for these two species was most likely a result of differences in the types of seed predators that attacked these two species. 相似文献
3.
4.
I Neuman A R Solano C Paz P Mele F Cornejo Maciel J R Lemos H N Fernandez E J Podesta 《The Journal of steroid biochemistry and molecular biology》1991,40(1-3):441-451
Luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) receptors are coupled to intracellular effector systems, most notably adenylate cyclase, through guanyl nucleotide-binding proteins or G-proteins. The molecular mechanism involved in the dynamic coupling of the LH/hCG receptor however, are not known. It has been postulated that receptor aggregation at the molecular level plays a critical role in this process. There have been attempts to understand the receptor association and dissociation phenomena at the molecular level. One of them involves the participation of the major histocompatibility complex (MHC) class I antigen in the mechanism of receptor activation and/or expression. One molecular basis for these mechanisms consists of a physical interaction between MHC proteins and receptors to form "compound receptors" able to transfer a hormonal signal to the cell. Using a photo-reactive probe we demonstrated that the LH/hCG receptors and the class I antigens are closely associated in the membrane. Thus, it is possible to form covalent complexes of hCG and class I antigens through the binding of the hormone to specific receptors. These findings imply that LH/hCG receptors and the MHC class I antigens may interact at the level of the plasma membrane in the mechanism of LH action. We also performed experiments using a single cell and limiting stimulation to a patch of membrane. The results stimulating the cell in a localized area suggested that even if all components are entirely free to float there is a constraint in the localization of the receptor, G-protein, and/or the effector, supporting the constraint dissociation model. Within a limited area subunits could dissociate, but they would not be free to diffuse throughout the membrane. Moreover the concept of compartmentalization that has been utilized to explain some inconsistencies in second-messenger action now can be proved by experimental design. 相似文献
5.
J Cornejo S I Beale M J Terry J C Lagarias 《The Journal of biological chemistry》1992,267(21):14790-14798
The unicellular rhodophyte, Porphyridium cruentum, and the filamentous cyanobacterium, Calothrix sp. PCC 7601, contain phycobiliproteins that have covalently bound phycobilin chromophores. Overnight incubation of solvent-extracted cells at 40 degrees C with methanol liberates free phycobilins that are derived from the protein-bound bilins by methanolytic cleavage of the thioether linkages between bilin and apoprotein. Two of the free bilins were identified as 3(E)-phycocyanobilin and 3(E)-phycoerythrombilin by comparative spectrophotometry and high pressure liquid chromatography. Methanolysis also yields a third bilin free acid whose absorption and 1H NMR spectra support the assignment of the 3(E)-phytochromobilin structure. This novel bilin is the major pigment isolated from cells that are pre-extracted with acetone-containing solvents. Since phytochrome- or phytochromobilin-containing proteins are not present in either organism, the 3(E)-phytochromobilin must arise by oxidation of phycobilin chromophores. This pigment is not obtained by similar treatment of a cyanobacterium and a rhodophyte that lack phycoerythrin. Therefore, 3(E)-phytochromobilin appears to be derived from phycoerythrobilin-containing proteins. Comparative CD spectroscopy of 3(E)-phytochrombilin and 3(E)-phycocyanobilin suggests that the two bilins share the R stereochemistry at the 2-position in the reduced pyrrole ring. Incubation of 2(R),3(E)-phytochromobilin with recombinant oat apophytochrome yields a covalent bilin adduct that is photoactive and spectrally indistinguishable from native oat phytochrome isolated from etiolated seedlings. These results establish that the phycobiliprotein-derived 2(R),3(E)-phytochromobilin is a biologically active phytochrome chromophore precursor. 相似文献
6.
Alberto Cornejo Julio Caballero Mario Simirgiotis Vanessa Torres Luisa Snchez Nicols Díaz Marcela Guimaraes Marcos Hernndez Carlos Areche Sergio Alfaro Leonardo Caballero Francisco Melo 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):154
Parkinson''s disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1. Also, aggregates treated with 1 do not provoke neurites'' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44. 相似文献
7.
CJ von Ruhland 《Biotechnic & histochemistry》2013,88(7):478-484
Amplification of immunohistochemical markers received considerable attention during the 1980s and 1990s. The amplification approach was largely abandoned following the development of antigen retrieval and reporter amplification techniques, because the latter were incorporated more easily into high throughput automated procedures in industrial and diagnostic laboratories. There remain, however, a number of instances where marker amplification still has much to offer. Consequently, we examined experimentally the utility of an optimized marker amplification technique in diagnostically relevant tissue where either the original signal strength was low or positive sites were visible, but sparsely distributed. Marker amplification in the former case not only improved the visibility of existing positive sites, but also revealed additional sites that previously were undetectable. In the latter case, positive sites were rendered more intense and therefore more easily seen during low magnification examination of large areas of tissue. 相似文献
8.
Gustavia johnclarkii and G. hubbardiorum, two new species from the wet forests of northwestern and Amazonian Ecuador, are described and illustrated. In addition, the two subspecies of both G. speciosa and G. macarenensis are elevated to species, and the new combination Gustavia paucisperma is provided. A justification for these changes is presented. 相似文献
9.
The experiment was organized in a 3×2 factorial arrangement with three dietary fat blends and a basal (20 mg kg?1 diet) or supplemented (220 mg kg?1) level of α-tocopheryl acetate. Dietary vitamin E and monounsaturated to polyunsaturated fatty acid ratio (dietary MUFA/PUFA) affected muscle α-tocopherol concentration (α-tocopherol [log μg g?1]=0.18 (±0.105)+0.0034 (±0.0003)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.39 (±0.122)·dietary MUFA/PUFA (P<0.0036)). An interaction between dietary α-tocopherol and dietary MUFA/PUFA exists for microsome α-tocopherol concentration (α-tocopherol [log μg g?1]=1.14 (±0.169) (P<0.0001)+0.0056 (±0.00099)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.54 (±0.206)·dietary MUFA/PUFA (P<0.0131)?0.0033 (±0.0011)·dietary α-tocopherol [mg kg?1)]×dietary MUFA/PUFA (P<0.0067)), and hexanal concentration in meat (hexanal [ng·g?1]=14807.9 (±1489.8)?28.8 (±10.6) dietary α-tocopherol [mg·kg?1] (P<0.01)?8436.6 (±1701.6)·dietary MUFA/PUFA (P<0.001)+24.0 (±11.22)·dietary α-tocopherol·dietary MUFA/PUFA (P<0.0416)). It is concluded that partial substitution of dietary PUFA with MUFA lead to an increase in the concentration of α-tocopherol in muscle and microsome extracts. An interaction between dietary α-tocopherol and fatty acids exists, in which at low level of dietary vitamin E inclusion, a low MUFA/PUFA ratio leads to a reduction in the concentration of α-tocopherol in microsome extracts and a concentration of hexanal in meat above the expected values. 相似文献
10.
Constanza Martínez Víctor Hugo Cornejo Pablo Lois Tammy Ellis Natalia P. Solis Brandon J. Wainwright Verónica Palma 《PloS one》2013,8(6)
The Sonic Hedgehog (Shh) pathway is responsible for critical patterning events early in development and for regulating the delicate balance between proliferation and differentiation in the developing and adult vertebrate brain. Currently, our knowledge of the potential role of Shh in regulating neural stem cells (NSC) is largely derived from analyses of the mammalian forebrain, but for dorsal midbrain development it is mostly unknown. For a detailed understanding of the role of Shh pathway for midbrain development in vivo, we took advantage of mouse embryos with cell autonomously activated Hedgehog (Hh) signaling in a conditional Patched 1 (Ptc1) mutant mouse model. This animal model shows an extensive embryonic tectal hypertrophy as a result of Hh pathway activation. In order to reveal the cellular and molecular origin of this in vivo phenotype, we established a novel culture system to evaluate neurospheres (nsps) viability, proliferation and differentiation. By recreating the three-dimensional (3-D) microenvironment we highlight the pivotal role of endogenous Shh in maintaining the stem cell potential of tectal radial glial cells (RGC) and progenitors by modulating their Ptc1 expression. We demonstrate that during late embryogenesis Shh enhances proliferation of NSC, whereas blockage of endogenous Shh signaling using cyclopamine, a potent Hh pathway inhibitor, produces the opposite effect. We propose that canonical Shh signaling plays a central role in the control of NSC behavior in the developing dorsal midbrain by acting as a niche factor by partially mediating the response of NSC to epidermal growth factor (EGF) and fibroblast growth factor (FGF) signaling. We conclude that endogenous Shh signaling is a critical mechanism regulating the proliferation of stem cell lineages in the embryonic dorsal tissue. 相似文献