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排序方式: 共有212条查询结果,搜索用时 187 毫秒
91.
92.
Thomas Kuhn Egon L Willighagen Achim Zielesny Christoph Steinbeck 《BMC bioinformatics》2010,11(1):159
Background
Small molecules are of increasing interest for bioinformatics in areas such as metabolomics and drug discovery. The recent release of large open access chemistry databases generates a demand for flexible tools to process them and discover new knowledge. To freely support open science based on these data resources, it is desirable for the processing tools to be open source and available for everyone. 相似文献93.
Carlsson K Persson E Carlsson U Svensson M 《Biochemical and biophysical research communications》2006,349(3):1111-1116
Blood coagulation is triggered by the formation of a complex between factor VIIa (FVIIa) and its cofactor, tissue factor (TF). The gamma-carboxyglutamic acid-rich domain of FVIIa docks with the C-terminal domain of TF, the EGF1 domain of FVIIa contacts both domains of TF, and the EGF2 domain and protease domain (PD) form a continuous surface that sits on the N-terminal domain of TF. Our aim was to investigate the conformational changes that occur in the sTF.PD binding region when different types of inhibitors, i.e., one active-site inhibitor (FFR-chloromethyl ketone (FFR)), two different peptide exosite inhibitors (E-76 and A-183), and the natural inhibitor tissue factor pathway inhibitor (TFPI), were allowed to bind to FVIIa. For this purpose, we constructed two sTF mutants (Q37C and E91C). By the aid of site-directed labeling technique, a fluorescent label was attached to the free cysteine. The sTF.PD interface was affected in position 37 by the binding of FFR, TFPI, and E-76, i.e., a more compact structure was sensed by the probe, while for position 91 located in the same region no change in the surrounding structure was observed. Thus, the active site inhibitors FFR and TFPI, and the exosite inhibitor E-76 have similar effects on the probe in position 37 of sTF, despite their differences in size and inhibition mechanism. The allosteric changes at the active site caused by binding of the exosite inhibitor E-76 in turn induce similar conformational changes in the sTF.PD interface as does the binding of the active site inhibitors. A-183, on the other hand, did not affect position 37 in sTF, indicating that the A-183 inhibition mechanism is different from that of E-76. 相似文献
94.
95.
Nikolay Natchev Patrick Lemell Egon Heiss Christian Beisser Josef Weisgram 《Zoomorphology》2010,129(2):111-119
The Indochinese box turtle Cuora galbinifrons is regarded as a purely terrestrial species, but our results demonstrate that it can feed both on land and in water. The
inverse relationship between the relative development of the hyoid apparatus and the tongue found in the most investigated
chelonians is not valid in the Indochinese box turtle. Our morphological analysis of the feeding apparatus reveals that the
palate shape and the design of the tongue are consistent with terrestrial feeders, but the construction of the hyoid complex
is more characteristic of aquatic feeders. Previous studies have demonstrated that tongue enlargement negatively impacts the
capacity of the turtles to suction feed. The present study focuses on the aquatic intraoral prey transport kinematic patterns.
Our analysis is based on high-speed films with 250 fr/s and high-speed cineradiography with 50 fr/s. The aquatic intraoral
food transport mechanisms differ depending on prey size: small items are transported predominantly by “inertial suction”,
whereas larger items are moved by the tongue—normally a clear terrestrial strategy. As the genus Cuora is ancestrally aquatic, the use of lingual food transport in the aquatic environment is presumably an aberrant modus typical
only for the most terrestrial among the Asian box turtles. 相似文献
96.
Sontag JM Nunbhakdi-Craig V Mitterhuber M Ogris E Sontag E 《Journal of neurochemistry》2010,115(6):1455-1465
Neuritic alterations are a major feature of many neurodegenerative disorders. Methylation of protein phosphatase 2A (PP2A) catalytic C subunit by the leucine carboxyl methyltransferase (LCMT1), and demethylation by the protein phosphatase methylesterase 1, is a critical PP2A regulatory mechanism. It modulates the formation of PP2A holoenzymes containing the Bα subunit, which dephosphorylate key neuronal cytoskeletal proteins, including tau. Significantly, we have reported that LCMT1, methylated C and Bα expression levels are down-regulated in Alzheimer disease-affected brain regions. In this study, we show that enhanced expression of LCMT1 in cultured N2a neuroblastoma cells, which increases endogenous methylated C and Bα levels, induces changes in F-actin organization. It promotes serum-independent neuritogenesis and development of extended tau-positive processes upon N2a cell differentiation. These stimulatory effects can be abrogated by LCMT1 knockdown and S-adenosylhomocysteine, an inhibitor of methylation reactions. Expression of protein phosphatase methylesterase 1 and the methylation-site L309Δ C subunit mutant, which decrease intracellular methylated C and Bα levels, block N2a cell differentiation and LCMT1-mediated neurite formation. Lastly, inducible and non-inducible knockdown of Bα in N2a cells inhibit process outgrowth. Altogether, our results establish a novel mechanistic link between PP2A methylation and development of neurite-like processes. 相似文献
97.
Karin Carlsson Egon Persson Mikael Lindgren Uno Carlsson Magdalena Svensson 《Biochemical and biophysical research communications》2011,(4):545
The apparent length of FVIIa in solution was estimated by a FRET analysis. Two fluorescent probes, fluorescein (Fl-FPR) and a rhodamine derivative (TMR), were covalently attached to FVIIa. The binding site of Fl-FPR was in the protease domain whereas TMR was positioned in the Gla domain, thus allowing a length measure over virtually the whole extension of the protein. From the FRET measurements, the distances between the two probes were determined to be 61.4 for free FVIIa and 65.5 Å for FVIIa bound to soluble tissue factor (sTF). These seemingly short distances, compared to those anticipated based on the complex crystal structure, require that the probes stretch towards each other. Thus, the apparent distance from the FRET analysis was shown to increase with 4 Å upon formation of a complex with sTF in solution. However, considering how protein dynamics, based on recent molecular dynamics simulations of FVIIa and sTF:FVIIa (Y.Z. Ohkubo, J.H. Morrissey, E. Tajkhorshid, J. Thromb. Haemost. 8 (2010) 1044–1053), can influence the apparent fluorescence signal our calculations indicated that the global average conformation of active-site inhibited FVIIa is nearly unaltered upon ligation to sTF.It is known from amidolytic activity measurements that Ca2+ binding leads to activation of FVIIa, but we have for the first time directly demonstrated conformational changes in the environment of the active site upon Ca2+ binding. Interestingly, this Ca2+-induced conformational change can be noted even in the presence of an inhibitor. Forming a complex with sTF further stabilized this conformational change, leading to a more inaccessible active-site located probe. 相似文献
98.
99.
Zuzuarregui A Kupka T Bhatt B Dohnal I Mudrak I Friedmann C Schüchner S Frohner IE Ammerer G Ogris E 《Nature methods》2012,9(6):594-596
We developed a protein-proximity assay in yeast based on fusing a histone lysine methyltransferase onto a bait and its substrate onto a prey. Upon binding, the prey is stably methylated and detected by methylation-specific antibodies. We applied this approach to detect varying interaction affinities among proteins in a mitogen-activated protein kinase pathway and to detect short-lived interactions between protein phosphatase 2A and its substrates that have so far escaped direct detection. 相似文献
100.
800 to 1,000 cases of traumatic spinal cord injury (S.C.I.) are observed in France each year. At present time, there are more than 35,000 survivors of S.C.I. in France. Studies show that 80% of injuries occur in men and 82% occur in individuals between the ages of 16 and 45 years. It is well known that more than 80% of men with S.C.I. suffer from ejaculation dysfunction. Since most of these couples are young, many desire a family and seek help to remedy their infertility. Two methods are mainly used to retrieve sperm from S.C.I. men: penile vibratory stimulation and rectal electrostimulation. Penile vibratory stimulation to induce ejaculation is recommended as first-line treatment, and S.C.I. men should only be referred for electroejaculation after failure of this technique. More than 70% of patients respond to penile vibratory stimulation with anterograde ejaculation. Patients who fail to ejaculate by penile vibratory stimulation are treated by electroejaculation. Their ejaculates often have normal sperm counts, but with a higher proportion of immotile sperm than in men without S.C.I. The authors report the pregnancy outcome of a series of 9 couples undergoing combined electroejaculation and in vitro fertilization with intracytoplasmic sperm injection: 25% pregnancies per cycle and 33% pregnancies per couple. 相似文献