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排序方式: 共有90条查询结果,搜索用时 31 毫秒
41.
42.
Thayer SP di Magliano MP Heiser PW Nielsen CM Roberts DJ Lauwers GY Qi YP Gysin S Fernández-del Castillo C Yajnik V Antoniu B McMahon M Warshaw AL Hebrok M 《Nature》2003,425(6960):851-856
Hedgehog signalling--an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer--may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis. 相似文献
43.
Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response 总被引:15,自引:0,他引:15
Garlanda C Hirsch E Bozza S Salustri A De Acetis M Nota R Maccagno A Riva F Bottazzi B Peri G Doni A Vago L Botto M De Santis R Carminati P Siracusa G Altruda F Vecchi A Romani L Mantovani A 《Nature》2002,420(6912):182-186
Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus. 相似文献
44.
Chicurel M 《Nature》2002,419(6908):751, 753, 755 passim
45.
46.
Sánchez-Hidalgo M Montalbán-López M Cebrián R Valdivia E Martínez-Bueno M Maqueda M 《Cellular and molecular life sciences : CMLS》2011,68(17):2845-2857
Bacteriocin AS-48 is an intriguing molecule because of its unique structural characteristics, genetic regulation, broad activity
spectrum, and potential biotechnological applications. It was the first reported circular bacteriocin and has been undoubtedly
the best characterized for the last 25 years. Thus, AS-48 is the prototype of circular bacteriocins (class IV), for which
the structure and genetic regulation have been elucidated. This review discusses the state-of-the-art in genetic engineering
with regard to this circular protein, with the use of site-directed mutagenesis and circular permutation. Mutagenesis studies
have been used to unravel the role of (a) different residues in the biological activity, underlining the relevance of several
residues involved in membrane interaction and the low correlation between stability and activity and (b) three amino acids
involved in maturation, providing information on the specificity of the leader peptidase and the circularization process itself.
To investigate the role of circularity in the stability and biological properties of the enterocin AS-48, two different ways
of linearization have been attempted: in vitro by limited proteolysis experiments and in vivo by circular permutation in the
structural gene as-48A. The results summarized here show the significance of circularization on the secondary structure, potency and, especially,
the stability of AS-48 and point as well to a putative role of the leader peptide as a protecting moiety in the pre-proprotein.
Taken all together, the data available on circular bacteriocins support the idea that AS-48 has been engineered by nature
to make a remarkably active and stable protein with a broad spectrum of activity. 相似文献
47.
Amaiden MR Santander VS Monesterolo NE Campetelli AN Rivelli JF Previtali G Arce CA Casale CH 《Cellular and molecular life sciences : CMLS》2011,68(10):1755-1768
The presence of tubulin in human erythrocytes was demonstrated using five different antibodies. Tubulin was distributed among
three operationally distinguishable pools: membrane, sedimentable structure and soluble fraction. It is known that in erythrocytes
from hypertensive subjects (HS), the Na+, K+-ATPase (NKA) activity is partially inhibited as compared with erythrocytes from normal subjects (NS). In erythrocytes from
HS the membrane tubulin pool is increased by ~150%. NKA was found to be forming a complex with acetylated tubulin that results
in inhibition of enzymes. This complex was also increased in erythrocytes from HS. Treatment of erythrocytes from HS with
nocodazol caused a decrease of acetylated tubulin in the membrane and stimulation of NKA activity, whereas taxol treatment
on erythrocytes from NS had the opposite effect. These results suggest that, in erythrocytes from HS, tubulin was translocated
to the membrane, where it associated with NKA with the consequent enzyme inhibition. 相似文献
48.
49.
Silvia Ravera Marina Podestà Federica Sabatini Chiara Fresia Marta Columbaro Silvia Bruno Ezio Fulcheri Luca Antonio Ramenghi Francesco Frassoni 《Cellular and molecular life sciences : CMLS》2018,75(5):889-903
We evaluated the energy metabolism of human mesenchymal stem cells (MSC) isolated from umbilical cord (UC) of preterm (< 37 weeks of gestational age) and term (≥ 37 weeks of gestational age) newborns, using MSC from adult bone marrow as control. A metabolic switch has been observed around the 34th week of gestational age from a prevalently anaerobic glycolysis to the oxidative phosphorylation. This metabolic change is associated with the organization of mitochondria reticulum: preterm MSCs presented a scarcely organized mitochondrial reticulum and low expression of proteins involved in the mitochondrial fission/fusion, compared to term MSCs. These changes seem governed by the expression of CLUH, a cytosolic messenger RNA-binding protein involved in the mitochondria biogenesis and distribution inside the cell; in fact, CLUH silencing in term MSC determined a metabolic fingerprint similar to that of preterm MSC. Our study discloses novel information on the production of energy and mitochondrial organization and function, during the passage from fetal to adult life, providing useful information for the management of preterm birth. 相似文献
50.
Lisa Seipold Hermann Altmeppen Tomas Koudelka Andreas Tholey Petr Kasparek Radislav Sedlacek Michaela Schweizer Julia Bär Marina Mikhaylova Markus Glatzel Paul Saftig 《Cellular and molecular life sciences : CMLS》2018,75(17):3251-3267
A disintegrin and metalloproteinase 10 (ADAM10) plays a major role in the ectodomain shedding of important surface molecules with physiological and pathological relevance including the amyloid precursor protein (APP), the cellular prion protein, and different cadherins. Despite its therapeutic potential, there is still a considerable lack of knowledge how this protease is regulated. We have previously identified tetraspanin15 (Tspan15) as a member of the TspanC8 family to specifically associate with ADAM10. Cell-based overexpression experiments revealed that this binding affected the maturation process and surface expression of the protease. Our current study shows that Tspan15 is abundantly expressed in mouse brain, where it specifically interacts with endogenous ADAM10. Tspan15 knockout mice did not reveal an overt phenotype but showed a pronounced decrease of the active and mature form of ADAM10, an effect which augmented with aging. The decreased expression of active ADAM10 correlated with an age-dependent reduced shedding of neuronal (N)-cadherin and the cellular prion protein. APP α-secretase cleavage and the expression of Notch-dependent genes were not affected by the loss of Tspan15, which is consistent with the hypothesis that different TspanC8s cause ADAM10 to preferentially cleave particular substrates. Analyzing spine morphology revealed no obvious differences between Tspan15 knockout and wild-type mice. However, Tspan15 expression was elevated in brains of an Alzheimer’s disease mouse model and of patients, suggesting that upregulation of Tspan15 expression reflects a cellular response in a disease state. In conclusion, our data show that Tspan15 and most likely also other members of the TspanC8 family are central modulators of ADAM10-mediated ectodomain shedding in vivo. 相似文献