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101.
102.
Thyroid Hormones Reorganize the Cytoskeleton of Glial Cells Through Gfap Phosphorylation and Rhoa-Dependent Mechanisms 总被引:1,自引:0,他引:1
Zamoner A Funchal C Jacques-Silva MC Gottfried C Barreto Silva FR Pessoa-Pureur R 《Cellular and molecular neurobiology》2007,27(7):845-865
Thyroid hormones (3,5,3′-triiodo-l-thyronine, T3; 3,5,3′,5′-l-tetraiodothyronine, T4; TH) play crucial roles in the growth and differentiation of the central nervous system. In this study, we investigated the
actions of TH on proliferation, viability, cell morphology, in vitro phosphorylation of glial fibrillary acidic protein (GFAP)
and actin reorganization in C6 glioma cells. We first observe that long-term exposure to TH stimulates cell proliferation
without induce cell death. We also demonstrate that after 3, 6, 12, 18, and 24 h treatment with TH, C6 cells and cortical
astrocytes show a process-bearing shape. Furthermore, immunocytochemistry with anti-actin and anti-GFAP antibodies reveals
that TH induces reorganization of actin and GFAP cytoskeleton. We also observe an increased in vitro 32P incorporation into GFAP recovered into the high-salt Triton insoluble cytoskeletal fraction after 3 and 24 h exposure to
5×10−8 and 10−6 M T3, and only after 24 h exposure to 10−9 M T4. These results show a T3 action on the phosphorylating system associated to GFAP and suggest a T3-independent effect of T4 on this cytoskeletal protein. In addition, C6 cells and astrocytes treated with lysophosphatidic acid, an upstream activator
of the RhoA GTPase pathway, totally prevented the morphological alterations induced by TH, indicating that this effect could
be mediated by the RhoA signaling pathway. Considering that IF network can be regulated by phosphorylation leading to reorganization
of IF filamentous structure and that alterations of the microfilament organization may have important implications in glial
functions, the effects of TH on glial cell cytoskeleton could be implicated in essential neural events such as brain development. 相似文献
103.
The solution structure of the C-terminal Domain V of the τ subunit of E. coli DNA polymerase III was determined by nuclear magnetic resonance (NMR) spectroscopy. The fold is unique to τ subunits. Amino acid sequence conservation is pronounced for hydrophobic residues that form the structural core of the protein, indicating that the fold is representative for τ subunits from a wide range of different bacteria. The interaction between the polymerase subunits τ and α was studied by NMR experiments where α was incubated with full-length C-terminal domain (τC16), and domains shortened at the C-terminus by 11 and 18 residues, respectively. The only interacting residues were found in the C-terminal 30-residue segment of τ, most of which is structurally disordered in free τC16. Since the N- and C-termini of the structured core of τC16 are located close to each other, this limits the possible distance between α and the pentameric δτ2γδ′ clamp–loader complex and, hence, between the two α subunits involved in leading- and lagging-strand DNA synthesis. Analysis of an N-terminally extended construct (τC22) showed that τC14 presents the only part of Domains IVa and V of τ which comprises a globular fold in the absence of other interaction partners. 相似文献
104.
Jergic S Ozawa K Williams NK Su XC Scott DD Hamdan SM Crowther JA Otting G Dixon NE 《Nucleic acids research》2007,35(9):2813-2824
The τ subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the α subunit through its C-terminal Domain V, τC16. We show that the extreme C-terminal region of τC16 constitutes the site of interaction with α. The τC16 domain, but not a derivative of it with a C-terminal deletion of seven residues (τC16Δ7), forms an isolable complex with α. Surface plasmon resonance measurements were used to determine the dissociation constant (KD) of the α−τC16 complex to be ~260pM. Competition with immobilized τC16 by τC16 derivatives for binding to α gave values of KD of 7μM for the α−τC16Δ7 complex. Low-level expression of the genes encoding τC16 and τC167, but not τC16Δ11, is lethal to E. coli. Suppression of this lethal phenotype enabled selection of mutations in the 3′ end of the τC16 gene, that led to defects in α binding. The data suggest that the unstructured C-terminus of τ becomes folded into a helix–loop–helix in its complex with α. An N-terminally extended construct, τC24, was found to bind DNA in a salt-sensitive manner while no binding was observed for τC16, suggesting that the processivity switch of the replisome functionally involves Domain IV of τ. 相似文献
105.
Holzapfel E Eisner G Alami M Barrett CM Buchanan G Lüke I Betton JM Robinson C Palmer T Moser M Müller M 《Biochemistry》2007,46(10):2892-2898
Translocation of twin-arginine precursor proteins across the cytoplasmic membrane of Escherichia coli requires the three membrane proteins TatA, TatB, and TatC. TatC and TatB were shown to be involved in precursor binding. We have analyzed in vitro a number of single alanine substitutions in tatC that were previously shown to compromise in vivo the function of the Tat translocase. All tatC mutants that were defective in precursor translocation into cytoplasmic membrane vesicles concomitantly interfered with precursor binding not only to TatC but also to TatB. Hence structural changes of TatC that affect precursor targeting simultaneously abolish engagement of the twin-arginine signal sequence with TatB and block the formation of a functional Tat translocase. Since these phenotypes were observed for tatC mutations spread over the first half of TatC, this entire part of the molecule must globally be involved in precursor binding. 相似文献
106.
Svea Dittmann Annika Schmid Susanna Richter Konrad Trülzsch Jürgen Heesemann Gottfried Wilharm 《BMC microbiology》2007,7(1):67
Background
Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica) share a virulence plasmid encoding a type three secretion system (T3SS). This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins), the specific Yop chaperones (Sycs), and the Ysc (Yop secretion) proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study. 相似文献107.
108.
Paramagnetic relaxation enhancements from unpaired electrons observed in nuclear magnetic resonance (NMR) spectra present
powerful long-range distance restraints. The most frequently used paramagnetic tags, however, are tethered to the protein
via disulfide bonds, requiring proteins with single cysteine residues for covalent attachment. Here we present a straightforward
strategy to tag proteins site-specifically with paramagnetic lanthanides without a tether and independent of cysteine residues.
It relies on preferential binding of the complex between three dipicolinic acid molecules (DPA) and a lanthanide ion (Ln3+), [Ln(DPA)3]3−, to a pair of positively charged amino acids whose charges are not compensated by negatively charged residues nearby. This
situation rarely occurs in wild-type proteins, allowing the creation of specific binding sites simply by introduction of positively
charged residues that are positioned far from glutamate or aspartate residues. The concept is demonstrated with the hnRNPLL
RRM1 domain. In addition, we show that histidine- and arginine-tags present binding sites for [Ln(DPA)3]3−. 相似文献
109.
Zeck A Pohlentz G Schlothauer T Peter-Katalinić J Regula JT 《Journal of proteome research》2011,10(7):3031-3039
Human leukocyte receptor IIIa (hFcγRIIIa) plays a prominent role in the elimination of tumor cells by antibody-based cancer therapies. In previous studies, a major impact of the presence of carbohydrates at Asn-162 on the binding between the receptor and the Fc part of wild type fucosylated or glycoengineered nonfucosylated antibodies has been shown. In this study, we performed a site directed carbohydrate analysis at hFcγRIIIa derived from human embryonic kidney (HEK) and Chinese hamster ovary (CHO) cells, respectively. Using mass spectrometry (MS) and a multienzyme protein digest, we analyzed the proteolysis-generated glycopeptides in detail. We could show that hFcγRIIIa expressed by HEK cells was mostly bearing multifucosylated biantennary Asn162-glycans with a major fraction terminating with GalNAc residues replacing the more common Gal. We could demonstrate that the glycan antennae with terminal GalNAc could be sialylated as indicated by a novel reporter ion HexNAcHexNAcNeuAc(+) (m/z 698.28) using a source induced dissociation (SID) scan in the MS cycle. In contrast to the hFcγRIIIa Asn-162 glycosylation pattern from HEK cells, the CHO cells derived receptor contains bi- and triantennary galactosylated and highly sialylated carbohydrates. Our data suggest that the type of expression host system was a dominating factor for formation of distinct glycopatterns of hFcγRIIIa, while the protein sequence and the site of glycosylation remained unchanged for both types of cells. Using surface plasmon resonance (SPR) interaction analysis, we show that the cell type and site specific glycosylation pattern of hFcγRIIIa influences its binding behavior to immunoglobulin molecules. 相似文献
110.
We collected urine samples from seven male bonobos (Pan paniscus) in the Eyengo community, Lomako Forest, Democratic Republic of Congo, and assayed them for testosterone (T). T levels averaged 525 pmol/mg Cr in adult males, and 309 pmol/mg Cr in subadult males. We collected hormonal and behavioral data during a period of relative social instability following the recent arrival of two immigrant males. In concordance with predictions derived from the challenge hypothesis [Wingfield et al., American Naturalist 136:829-846, 1990], which relates T to levels of reproductive aggression, the alpha male had the highest circulating levels of T. When we removed the two recent immigrant males from the analysis, there was a significant positive correlation between T levels and dominance rank for the long-term resident males (n=5, P=0.001, r2=0.98). These are the first data on T levels in wild bonobos, and the results suggest that further study of the relationship between T levels and social context in this species could inform current models relating hormones and aggression in wild apes. 相似文献