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311.
Rentetzi M 《Annals of science》2011,68(3):375-399
This article discusses the intersection of science and culture in the marketplace and explores the ways in which radium quack and medicinal products were packaged and labelled in the early twentieth century US. Although there is an interesting growing body of literature by art historians on package design, historians of science and medicine have paid little to no attention to the ways scientific and medical objects that were turned into commodities were packaged and commercialized. Thinking about packages not as mere containers but as multifunctional tools adds to historical accounts of science as a sociocultural enterprise and reminds us that science has always been part of consumer culture. This paper suggests that far from being receptacles that preserve their content and facilitate their transportation, bottles and boxes that contained radium products functioned as commercial and epistemic devices. It was the 1906 Pure Food and Drug Act that enforced such functions. Packages worked as commercial devices in the sense that they were used to boost sales. In addition, 'epistemic' points to the fact that the package is an artefact that ascribes meaning to and shapes its content while at the same time working as a device for distinguishing between patent and orthodox medicines. 相似文献
312.
Piontek J Fritzsche S Cording J Richter S Hartwig J Walter M Yu D Turner JR Gehring C Rahn HP Wolburg H Blasig IE 《Cellular and molecular life sciences : CMLS》2011,68(23):3903-3918
Paracellular barrier properties of tissues are mainly determined by the composition of claudin heteropolymers. To analyze the molecular organization of tight junctions (TJ), we investigated the ability of claudins (Cld) to form homo- and heteromers. Cld1, -2, -3, -5, and -12 expressed in cerebral barriers were investigated. TJ-strands were reconstituted by claudin-transfection of HEK293-cells. cis-Interactions and/or spatial proximity were analyzed by fluorescence resonance energy transfer inside and outside of strands and ranked: Cld5/Cld5?>?Cld5/Cld1?>?Cld3/Cld1?>?Cld3/Cld3?>?Cld3/Cld5, no Cld3/Cld2. Classic Cld1, -3, and -5 but not non-classic Cld12 showed homophilic trans-interaction. Freeze-fracture electron microscopy revealed that, in contrast to classic claudins, YFP-tagged Cld12 does not form homopolymers. Heterophilic trans-interactions were analyzed in cocultures of differently monotransfected cells. trans-Interaction of Cld3/Cld5 was less pronounced than that of Cld3/Cld1, Cld5/Cld1, Cld5/Cld5 or Cld3/Cld3. The barrier function of reconstituted TJ-strands was demonstrated by a novel imaging assay. A model of the molecular organization of TJ was generated. 相似文献
313.
Ferrante MI Zullo A Barra A Bimonte S Messaddeq N Studer M Dollé P Franco B 《Nature genetics》2006,38(1):112-117
The oral-facial-digital type I (OFD1) syndrome (OMIM 311200) is a human developmental disorder; affected individuals have craniofacial and digital abnormalities and, in 15% of cases, polycystic kidney. The disease is inherited as an X-linked dominant male-lethal trait. Using a Cre-loxP system, we generated knockout animals lacking Ofd1 and reproduced the main features of the disease, albeit with increased severity, possibly owing to differences of X inactivation patterns between human and mouse. We found failure of left-right axis specification in mutant male embryos, and ultrastructural analysis showed a lack of cilia in the embryonic node. Formation of cilia was defective in cystic kidneys from heterozygous females, implicating ciliogenesis as a mechanism underlying cyst development. In addition, we found impaired patterning of the neural tube and altered expression of the 5' Hoxa and Hoxd genes in the limb buds of mice lacking Ofd1, suggesting that Ofd1 could have a role beyond primary cilium organization and assembly. 相似文献
314.
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome 总被引:15,自引:0,他引:15
Niihori T Aoki Y Narumi Y Neri G Cavé H Verloes A Okamoto N Hennekam RC Gillessen-Kaesbach G Wieczorek D Kavamura MI Kurosawa K Ohashi H Wilson L Heron D Bonneau D Corona G Kaname T Naritomi K Baumann C Matsumoto N Kato K Kure S Matsubara Y 《Nature genetics》2006,38(3):294-296
Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders. 相似文献
315.
Anna Maria Frassanito Laura Barsanti Vincenzo Passarelli Valtere Evangelista Paolo Gualtieri 《Cellular and molecular life sciences : CMLS》2010,67(6):965-971
Here, we report the DNA sequence of the rhodopsin gene in the alga Cyanophora paradoxa (Glaucophyta). The primers were designed according to the conserved regions of prokaryotic and eukaryotic rhodopsin-like
proteins deposited in the GenBank. The sequence consists of 1,272 bp comprised of 5 introns. The correspondent protein, named
Cyanophopsin, showed high identity to rhodopsin-like proteins of Archea, Bacteria, Fungi, and Algae. At the N-terminal, the
protein is characterized by a region with no transmembrane α-helices (80 aa), followed by a region with 7α-helices (219 aa)
and a shorter 35-aa C-terminal region. The DNA sequence of the N-terminal region was expressed in E. coli and the recombinant purified peptide was used as antigen in hens to obtain polyclonal antibodies. Indirect immunofluorescence
in C. paradoxa cells showed a marked labeling of the muroplast (aka cyanelle) membrane. 相似文献
316.
Daniela Corda Pasquale Zizza Alessia Varone Beatrice Maria Filippi Stefania Mariggiò 《Cellular and molecular life sciences : CMLS》2009,66(21):3449-3467
The glycerophosphoinositols are cellular products of phospholipase A2 and lysolipase activities on the membrane phosphoinositides. Their intracellular concentrations can vary upon oncogenic transformation,
cell differentiation and hormonal stimulation. Specific glycerophosphodiester phosphodiesterases are involved in their catabolism,
which, as with their formation, is under hormonal regulation. With their mechanisms of action including modulation of adenylyl
cyclase, intracellular calcium levels, and Rho-GTPases, the glycerophosphoinositols have diverse effects in multiple cell
types: induction of cell proliferation in thyroid cells; modulation of actin cytoskeleton organisation in fibroblasts; and
reduction of the invasive potential of tumour cell lines. More recent investigations include their effects in inflammatory
and immune responses. Indeed, the glycerophosphoinositols enhance cytokine-dependent chemotaxis in T-lymphocytes induced by
SDF-1α-receptor activation, indicating roles for these compounds as modulators of T-cell signalling and T-cell responses. 相似文献
317.
Sarno S Mazzorana M Traynor R Ruzzene M Cozza G Pagano MA Meggio F Zagotto G Battistutta R Pinna LA 《Cellular and molecular life sciences : CMLS》2012,69(3):449-460
8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of
protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter
as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as
“denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC50 > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases
that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC50 values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural
features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit
of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68
and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved
water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to
the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A
by dNBC. 相似文献
318.
Curnis F Gasparri AM Longhi R Colombo B D'Alessio S Pastorino F Ponzoni M Corti A 《Cellular and molecular life sciences : CMLS》2012,69(16):2791-2803
Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, neurons, cardiomyocytes, and keratinocytes, is the precursor of various peptides that regulate the carbohydrate/lipid metabolism and the cardiovascular system. We have found that CgA, locally administered to injured mice, can accelerate keratinocyte proliferation and wound healing. This biological activity was abolished by the Asp(45)Glu mutation. CgA and its N-terminal fragments, but not the corresponding Asp(45)Glu mutants, could selectively recognize the αvβ6-integrin on keratinocytes (a cell-adhesion receptor that is up-regulated during wound healing) and regulate keratinocyte adhesion, proliferation, and migration. No binding was observed to other integrins such as αvβ3, αvβ5, αvβ8, α5β1, α1β1, α3β1, α6β4, α6β7 and α9β1. Structure-activity studies showed that the entire CgA(39-63) region is crucial for αvβ6 recognition (K(i) = 7 nM). This region contains an RGD site (residues CgA(43-45)) followed by an amphipathic α-helix (residues CgA(47-63)), both crucial for binding affinity and selectivity. These results suggest that the interaction of the RGD/α-helix motif of CgA with αvβ6 regulates keratinocyte physiology in wound healing. 相似文献
319.
RA Scott V Lagou RP Welch E Wheeler ME Montasser J Luan R Mägi RJ Strawbridge E Rehnberg S Gustafsson S Kanoni LJ Rasmussen-Torvik L Yengo C Lecoeur D Shungin S Sanna C Sidore PC Johnson JW Jukema T Johnson A Mahajan N Verweij G Thorleifsson JJ Hottenga S Shah AV Smith B Sennblad C Gieger P Salo M Perola NJ Timpson DM Evans BS Pourcain Y Wu JS Andrews J Hui LF Bielak W Zhao M Horikoshi P Navarro A Isaacs JR O'Connell K Stirrups V Vitart C Hayward T Esko E Mihailov RM Fraser T Fall BF Voight 《Nature genetics》2012,44(9):991-1005
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. 相似文献
320.
Paternoster L Standl M Chen CM Ramasamy A Bønnelykke K Duijts L Ferreira MA Alves AC Thyssen JP Albrecht E Baurecht H Feenstra B Sleiman PM Hysi P Warrington NM Curjuric I Myhre R Curtin JA Groen-Blokhuis MM Kerkhof M Sääf A Franke A Ellinghaus D Fölster-Holst R Dermitzakis E Montgomery SB Prokisch H Heim K Hartikainen AL Pouta A Pekkanen J Blakemore AI Buxton JL Kaakinen M Duffy DL Madden PA Heath AC Montgomery GW Thompson PJ Matheson MC Le Souëf P;Australian Asthma Genetics Consortium 《Nature genetics》2012,44(2):187-192
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis. 相似文献