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171.
Shizhong Li Teresa Torre-Muruzabal Karen C. S?gaard Guilin R. Ren Frank Hauser Signe M. Engelsen Mads D. P?denphanth Annick Desjardins Cornelis J. P. Grimmelikhuijzen 《PloS one》2013,8(10)
The insect neuropeptides CCHamide-1 and -2 are recently discovered peptides that probably occur in all arthropods. Here, we used immunocytochemistry, in situ hybridization, and quantitative PCR (qPCR), to localize the two peptides in the fruitfly Drosophila melanogaster. We found that CCHamide-1 and -2 were localized in endocrine cells of the midgut of larvae and adult flies. These endocrine cells had the appearance of sensory cells, projecting processes close to or into the gut lumen. In addition, CCHamide-2 was also localized in about forty neurons in the brain hemispheres and ventral nerve cord of larvae. Using qPCR we found high expression of the CCHamide-2 gene in the larval gut and very low expression of its receptor gene, while in the larval brain we found low expression of CCHamide-2 and very high expression of its receptor. These expression patterns suggest the following model: Endocrine CCHamide-2 cells in the gut sense the quality of food components in the gut lumen and transmit this information to the brain by releasing CCHamide-2 into the circulation; subsequently, after binding to its brain receptors, CCHamides-2 induces an altered feeding behavior in the animal and possibly other homeostatic adaptations. 相似文献
172.
Jarid1b targets genes regulating development and is involved in neural differentiation 总被引:1,自引:0,他引:1
Schmitz SU Albert M Malatesta M Morey L Johansen JV Bak M Tommerup N Abarrategui I Helin K 《The EMBO journal》2011,30(22):4586-4600
173.
Andersen RS Sørensen RB Ritter C Svane IM Becker JC thor Straten P Andersen MH 《Cancer immunology, immunotherapy : CII》2011,60(2):227-234
With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms
to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high
HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic
cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific
manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients
and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with
breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the
peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer
patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently
detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL
epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses
in cancer patients and healthy donors. 相似文献
174.
175.
176.
Nybo M Nielsen LB Nielsen SJ Lindegaard M Damm P Rehfeld JF Goetze JP 《Regulatory peptides》2007,141(1-3):135-139
BACKGROUND: Maternal diabetes increases the risk of hypertrophic cardiomyopathy in the fetus. As signaling via the C-type natriuretic peptide (CNP) specific receptor protects against cardiac hypertrophy, we examined whether maternal type 1 diabetes affects the plasma concentrations of proCNP-derived peptides in newborn infants. METHODS: Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. RESULTS: The median proCNP concentrations were similar in umbilical cord plasma from pregnant women with and without type 1 diabetes (17 pmol/L vs. 19 pmol/L, P not significant) and did not correlate with the proBNP concentrations in the same samples. However, the molar ratio between the proCNP and the CNP peptide was increased in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. CONCLUSIONS: There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ from healthy adults. The precise mechanism underlying these differences warrants further investigation. 相似文献
177.
Sørensen RB Hadrup SR Køllgaard T Svane IM thor Straten P Andersen MH 《Cancer immunology, immunotherapy : CII》2007,56(4):527-533
Based on the detection of spontaneous immune responses in cancer patients with cancer of different origin, Bcl-X(L) was recently
described as a highly interesting tumor antigen recognized by CD8 positive cytotoxic T lymphocytes. To further characterize
Bcl-X(L) as a tumor antigen we isolated and expanded Bcl-X(L) specific T cells from the peripheral blood of a breast cancer
patient hosting a strong Bcl-X(L) specific T cell response. We describe that HLA-A2 restricted Bcl-X(L) specific T cell clones
very efficiently lyse peptide pulsed T2 cells. Furthermore, tumor cell lines of different origin, i.e., breast cancer, colon
cancer, and melanoma, are efficiently lysed in an HLA-dependent manner. Finally, ex vivo-isolated leukemia cells, but not
non-malignant B and T cells are killed by Bcl-X(L) specific T cells. Our data underline Bcl-X(L) as an universal tumor antigen
widely applicable in specific anticancer immunotherapy. 相似文献
178.
Mads T. S?ndergaard Xixi Tian Yingjie Liu Ruiwu Wang Walter J. Chazin S. R. Wayne Chen Michael T. Overgaard 《The Journal of biological chemistry》2015,290(43):26151-26162
The intracellular Ca2+ sensor calmodulin (CaM) regulates the cardiac Ca2+ release channel/ryanodine receptor 2 (RyR2), and mutations in CaM cause arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome. Here, we investigated the effect of CaM mutations causing CPVT (N53I), long QT syndrome (D95V and D129G), or both (CaM N97S) on RyR2-mediated Ca2+ release. All mutations increased Ca2+ release and rendered RyR2 more susceptible to store overload-induced Ca2+ release (SOICR) by lowering the threshold of store Ca2+ content at which SOICR occurred and the threshold at which SOICR terminated. To obtain mechanistic insights, we investigated the Ca2+ binding of the N- and C-terminal domains (N- and C-domain) of CaM in the presence of a peptide corresponding to the CaM-binding domain of RyR2. The N53I mutation decreased the affinity of Ca2+ binding to the N-domain of CaM, relative to CaM WT, but did not affect the C-domain. Conversely, mutations N97S, D95V, and D129G had little or no effect on Ca2+ binding to the N-domain but markedly decreased the affinity of the C-domain for Ca2+. These results suggest that mutations D95V, N97S, and D129G alter the interaction between CaM and the CaMBD and thus RyR2 regulation. Because the N53I mutation minimally affected Ca2+ binding to the C-domain, it must cause aberrant regulation via a different mechanism. These results support aberrant RyR2 regulation as the disease mechanism for CPVT associated with CaM mutations and shows that CaM mutations not associated with CPVT can also affect RyR2. A model for the CaM-RyR2 interaction, where the Ca2+-saturated C-domain is constitutively bound to RyR2 and the N-domain senses increases in Ca2+ concentration, is proposed. 相似文献
179.
Christoph Biesemann Mads Grønborg Elisa Luquet Sven P Wichert Véronique Bernard Simon R Bungers Ben Cooper Frédérique Varoqueaux Liyi Li Jennifer A Byrne Henning Urlaub Olaf Jahn Nils Brose Etienne Herzog 《The EMBO journal》2014,33(2):157-170
For decades, neuroscientists have used enriched preparations of synaptic particles called synaptosomes to study synapse function. However, the interpretation of corresponding data is problematic as synaptosome preparations contain multiple types of synapses and non‐synaptic neuronal and glial contaminants. We established a novel Fluorescence Activated Synaptosome Sorting (FASS) method that substantially improves conventional synaptosome enrichment protocols and enables high‐resolution biochemical analyses of specific synapse subpopulations. Employing knock‐in mice with fluorescent glutamatergic synapses, we show that FASS isolates intact ultrapure synaptosomes composed of a resealed presynaptic terminal and a postsynaptic density as assessed by light and electron microscopy. FASS synaptosomes contain bona fide glutamatergic synapse proteins but are almost devoid of other synapse types and extrasynaptic or glial contaminants. We identified 163 enriched proteins in FASS samples, of which FXYD6 and Tpd52 were validated as new synaptic proteins. FASS purification thus enables high‐resolution biochemical analyses of specific synapse subpopulations in health and disease. 相似文献
180.
Mads F. Hjorth Jean-Philippe Chaput Camilla T. Damsgaard Stine-Mathilde Dalskov Rikke Andersen Arne Astrup Kim F. Michaelsen Inge Tetens Christian Ritz Anders Sj?din 《PloS one》2014,9(8)