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161.
N. Helge Meyer Hubert Mayerhofer Konstantinos Tripsianes Silke Blindow Daniela Barths Astrid Mewes Thomas Weimar Thies K?hli Steffen Bade Tobias Madl Andreas Frey Helmut Haas Jochen Mueller-Dieckmann Michael Sattler Gabriele Schramm 《The Journal of biological chemistry》2015,290(36):22111-22126
The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism. 相似文献
162.
Thorsten Maretzky Astrid Evers Sylvain Le Gall Rolake O. Alabi Nancy Speck Karina Reiss Carl P. Blobel 《The Journal of biological chemistry》2015,290(12):7416-7425
The membrane-anchored metalloproteinase a disintegrin and metalloprotease 10 (ADAM10) is required for shedding of membrane proteins such as EGF, betacellulin, the amyloid precursor protein, and CD23 from cells. ADAM10 is constitutively active and can be rapidly and post-translationally enhanced by several stimuli, yet little is known about the underlying mechanism. Here, we use ADAM10-deficient cells transfected with wild type or mutant ADAM10 to address the role of its cytoplasmic and transmembrane domain in regulating ADAM10-dependent protein ectodomain shedding. We report that the cytoplasmic domain of ADAM10 negatively regulates its constitutive activity through an ER retention motif but is dispensable for its stimulated activity. However, chimeras with the extracellular domain of ADAM10 and the transmembrane domain of ADAM17 with or without the cytoplasmic domain of ADAM17 show reduced stimulated shedding of the ADAM10 substrate betacellulin, whereas the ionomycin-stimulated shedding of the ADAM17 substrates CD62-L and TGFα is not affected. Moreover, we show that influx of extracellular calcium activates ADAM10 but is not essential for its activation by APMA and BzATP. Finally, the rapid stimulation of ADAM10 is not significantly affected by incubation with proprotein convertase inhibitors for up to 8 h, arguing against a major role of increased prodomain removal in the rapid stimulation of ADAM10. Thus, the cytoplasmic domain of ADAM10 negatively influences constitutive shedding through an ER retention motif, whereas the cytoplasmic domain and prodomain processing are not required for the rapid activation of ADAM10-dependent shedding events. 相似文献
163.
164.
Dionne C.G. Klein Astrid Skjesol Esther D. Kers‐Rebel Tatyana Sherstova Bjrnar Sporsheim Kjartan W. Egeberg Bjrn T. Stokke Terje Espevik Harald Husebye 《Traffic (Copenhagen, Denmark)》2015,16(7):677-690
Toll‐like receptor 4 (TLR4) is responsible for the immediate response to Gram‐negative bacteria and signals via two main pathways by recruitment of distinct pairs of adaptor proteins. Mal‐MyD88 [Mal (MyD88‐adaptor‐like) ‐ MYD88 (Myeloid differentiation primary response gene (88))] is recruited to the plasma membrane to initiate the signaling cascade leading to production of pro‐inflammatory cytokines while TRAM‐TRIF [TRAM (TRIF‐related adaptor molecule)‐TRIF (TIR‐domain‐containing adapter‐inducing interferon‐β)] is recruited to early endosomes to initiate the subsequent production of type I interferons. We have investigated the dynamics of TLR4 and TRAM during lipopolysaccharide (LPS) stimulation. We found that LPS induced a CD14‐dependent immobile fraction of TLR4 in the plasma membrane. Total internal reflection fluorescence microscopy (TIRF) revealed that LPS stimulation induced clustering of TLR4 into small punctate structures in the plasma membrane containing CD14/LPS and clathrin, both in HEK293 cells and the macrophage model cell line U373‐CD14. These results suggest that laterally immobilized TLR4 receptor complexes are being formed and prepared for endocytosis. RAB11A was found to be involved in localizing TRAM to the endocytic recycling compartment (ERC) and to early sorting endosomes. Moreover, CD14/LPS but not TRAM was immobilized on RAB11A‐positive endosomes, which indicates that TRAM and CD14/LPS can independently be recruited to endosomes. 相似文献
165.
166.
167.
Windner SE Steinbacher P Obermayer A Kasiba B Zweimueller-Mayer J Stoiber W 《Development genes and evolution》2011,221(3):167-178
The formation of the body wall musculature in vertebrates is assumed to be initiated by direct ventral extension of the somites/myotomes.
This contrasts to the formation of limb muscles and muscles involved in feeding or respiration/ventilation, which are founded
by migratory muscle precursors (MMPs) distant to the somites. Here, we present evidence from morphology and expression of
molecular markers proposing that the formation of the two muscle layers of the teleost body wall involves both of the above
mechanisms: (1) MMPs from somites 5 and 6 found an independent muscle primordium–the so-called posterior hypaxial muscle (PHM)–which
subsequently gives rise to the most anterior two segments of the medial obliquus inferioris (OI) muscle. (2) Direct epithelial
extension of the hypaxial myotomes generates the OI segments from somite 7 caudalward and the entire lateral obliquus superioris
(OS) muscle. The findings are discussed in relation to the evolution of hypaxial myogenic patterning including functional
considerations. We hypothesise that the potential of the most anterior somites to generate migratory muscle precursors is
a general vertebrate feature that has been differently utilised in the evolution in vertebrate groups. 相似文献
168.
169.
Silviya Velichkova Wolkerstorfer Astrid Wonisch Tatiana Stankova Nikolina Tsvetkova Michael Tausz 《Trees - Structure and Function》2011,25(6):1043-1052
Seasonal changes in physiological and biochemical parameters were studied in 35-, 55- and 140-year-old trees of Turkey oak
(Quercus cerris L.) and Hungarian oak (Q. frainetto Ten.), growing in natural stands in Eastern Balkan Mountains (Bulgaria). During the seasonal drought period (August), assimilation
activity, transpiration rate, stomatal conductance and water potential had a seasonal minimum in all the studied tree ages
and species. The foliar concentrations of glutathione, ascorbate, α-tocopherol, as well as photosynthetic pigments in oak
leaves were significantly affected by season. With the increasing age of the studied trees, we observed a decrease of the
physiological activity and an increase of the antioxidants’ accumulation. Both the species were drought tolerant and anisohydric,
where Q. frainetto exhibited higher rates of gas exchange than Q. cerris. Moreover, they differed in the extent of increase in the foliar antioxidants and carotenoids. 相似文献
170.
Doebis C Menning A Neumann K Ghani S Schlawe K Lauer U Hamann A Huehn J Syrbe U 《Immunology and cell biology》2011,89(4):566-572
Although activation and subsequent expansion of naive CD4(+) T cells within lymph nodes is well characterized, the fate of T effector cells activated within peripheral tissues during secondary reactions is poorly defined. Therefore, we studied the recruitment, proliferation and egress of antigen-specific Th1 effector cells in comparison with nonspecific Th1 cells throughout a delayed-type hypersensitivity reaction (DTH). Although we observed a high turnover of Th1 effector cells with unspecific high-rate recruitment and CCR7-dependent egress from the inflamed tissue in the early, acute DTH phase, a strong, selective accumulation of antigen-specific T cells occurred during the chronic, late DTH phase. This was mainly based on local proliferation of CD4(+) effector cells within the DTH tissue and concomitant retention. Considering the strong CCR7-dependent Th cell egress found in this model, the reduced CCR7 expression on antigen-specific T cells isolated from late-phase DTH tissue most likely contributes to the retention of these cells within the tissue. Thus, peripheral tissues can support not only the proliferation of CD8(+) T cells, as recently shown, but also that of CD4(+) T effector cells, forming a pool of tissue-resident T cells. 相似文献