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31.
C. G. Casinovi G. Grandolini L. Radics C. Rossi 《Cellular and molecular life sciences : CMLS》1978,34(3):298-299
Summary From culture filtrates ofFusicoccum amygdali, Del., a new compound, whose structure corresponds to 1,2,3-trihydroxy-p-menthane, has been isolated. Its discovery is of some interest since, to our knowledge, it is the first time that a monoterpenoid is isolated from a microorganism. 相似文献
32.
The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely affected by high phospholipid-cholesterol ratios. 相似文献
33.
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35.
A. Ballio C. G. Casinovi G. Randazzo C. Rossi 《Cellular and molecular life sciences : CMLS》1970,26(4):349-351
Riassunto Dai brodi di coltura diFusicoccum amygdali Del. sono stati isolati un isomero della fusicoccina (isofusicoccina), una monodeacetilfusicoccina, in cui manca 1'acetile sul residuo del glucosio, e la dideacetilfusicoccina.
On leave from the Instituto di Chimica Farmaceutica e Tossico logica dell'Università di Perugia. 相似文献
On leave from the Instituto di Chimica Farmaceutica e Tossico logica dell'Università di Perugia. 相似文献
36.
R. Jaques G. Huber L. Neipp A. Rossi B. Schär R. Meier 《Cellular and molecular life sciences : CMLS》1967,23(2):149-150
Summary CIBA 21 401-Ba, a glucofuranoside derivative (ethyl-3,5,6-O-benzyl-d-glucofuranoside), antagonizes in vitro the smooth-muscle action of a large number of biogenic amines and polypeptides, the accelerated migration of leucocytes induced by endotoxin, and the Schultz-Dale phenomenon. In vivo, the compound shows anti-inflammatory and anti-allergic effects and improves the survival rate of infected mice treated with suboptimal doses of a sulphonamide. 相似文献
37.
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer 总被引:1,自引:0,他引:1
Misale S Yaeger R Hobor S Scala E Janakiraman M Liska D Valtorta E Schiavo R Buscarino M Siravegna G Bencardino K Cercek A Chen CT Veronese S Zanon C Sartore-Bianchi A Gambacorta M Gallicchio M Vakiani E Boscaro V Medico E Weiser M Siena S Di Nicolantonio F Solit D Bardelli A 《Nature》2012,486(7404):532-536
A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance. 相似文献
38.
Seo MD Velamakanni S Ishiyama N Stathopulos PB Rossi AM Khan SA Dale P Li C Ames JB Ikura M Taylor CW 《Nature》2012,483(7387):108-112
Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6??) and without (3.0??) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore. 相似文献
39.
Schattschneider P Rubino S Hébert C Rusz J Kunes J Novák P Carlino E Fabrizioli M Panaccione G Rossi G 《Nature》2006,441(7092):486-488
A material is said to exhibit dichroism if its photon absorption spectrum depends on the polarization of the incident radiation. In the case of X-ray magnetic circular dichroism (XMCD), the absorption cross-section of a ferromagnet or a paramagnet in a magnetic field changes when the helicity of a circularly polarized photon is reversed relative to the magnetization direction. Although similarities between X-ray absorption and electron energy-loss spectroscopy in a transmission electron microscope (TEM) have long been recognized, it has been assumed that extending such equivalence to circular dichroism would require the electron beam in the TEM to be spin-polarized. Recently, it was argued on theoretical grounds that this assumption is probably wrong. Here we report the direct experimental detection of magnetic circular dichroism in a TEM. We compare our measurements of electron energy-loss magnetic chiral dichroism (EMCD) with XMCD spectra obtained from the same specimen that, together with theoretical calculations, show that chiral atomic transitions in a specimen are accessible with inelastic electron scattering under particular scattering conditions. This finding could have important consequences for the study of magnetism on the nanometre and subnanometre scales, as EMCD offers the potential for such spatial resolution down to the nanometre scale while providing depth information--in contrast to X-ray methods, which are mainly surface-sensitive. 相似文献
40.
S. Ronca-Testoni S. Hrelia G. Hakim C. A. Rossi 《Cellular and molecular life sciences : CMLS》1985,41(1):75-76
Summary Some smooth muscle relaxant drugs with an unknown mechanism of action have been tested for their interaction with calmodulin and with calmodulin-induced cyclic nucleotide phosphodiesterase (PDE) activity. The affinity of these drugs for calmodulin does not parallel their inhibitory effect on the calmodulin activation of PDE. The lack of parallelism could be due to a binding of the drugs to different sites on calmodulin; furthermore a binding of papaverine, octylonium bromide and felodipine to PDE molecule, might also be considered to explain their inhibitory effect on PDE basal activity. The myolytic effect of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems. 相似文献