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141.
Chimeric receptors that include CD28 signaling in series with TCRzeta in the same receptor have been demonstrated to activate prestimulated human primary T cells more efficiently than a receptor providing TCRzeta signaling alone. We examined whether this type of receptor can also activate resting human primary T cells, and whether molecules other than CD28 could be included in a single chimeric receptor in series with TCRzeta to mediate the activation of resting human primary T cells. Human CD33-specific chimeric receptors were generated with CD28, inducible costimulator, CD134, or CD137 signaling regions in series with TCRzeta signaling region and transfected by electroporation into resting human primary T cells. Their ability to mediate Ag-specific activation was analyzed in comparison with a receptor providing TCRzeta signaling alone. Inclusion of any of the costimulatory signaling regions in series with TCRzeta enhanced the level of specific Ag-induced IL-2, IFN-gamma, TNF-alpha, and GM-CSF cytokine production and enabled resting primary T cells to survive and proliferate in response to Ag in the absence of any exogenous factors. Inclusion of CD28, inducible costimulator, or CD134 enhanced TCRzeta-mediated, Ag-specific target cell lysis. Chimeric receptors providing B7 and TNFR family costimulatory signals in series with TCRzeta in the same receptor can confer self-sufficient clonal expansion and enhanced effector function to resting human T cells. This type of chimeric receptor may now be used to discover the most potent combination of costimulatory signals that will improve current immunotherapeutic strategies. 相似文献
142.
Charlotte Noyer Alastair Hamilton Oriol Sacristan-Soriano Mikel Aingeru Becerro 《Symbiosis (Philadelphia, Pa.)》2010,51(3):239-243
Marine sponges can host in their tissues abundant and diverse bacterial communities. Lack of truly quantitative data on bacterial
abundance and dynamics limits our understanding of the organization and functioning of these endobiotic communities. In this
technical note, we describe a quantitative polymerase chain reaction approach to quantify the relative abundance of multiple
clades of three major sponge-associated bacterial phyla: Chloroflexi, Acidobacteria, and Actinobacteria. To test our approach we used the Mediterranean sponges Spongia lamella and Aplysina aerophoba. We designed five out of the six primer sets used in our study. We tested the new primer sets for specificity and optimized
their conditions. Our preliminary data showed that Spongia lamella had larger bacterial abundance than Aplysina aerophoba, except for one clade of Chloroflexi. The two Chloroflexi clades investigated in our study amplified a fraction of the Chloroflexi present in Spongia lamella and most of what is present in Aplysina aerophoba, suggesting a more diverse Chloroflexi population in Spongia lamella than in Aplysina aerophoba. This quantitative technique has a great potential to provide a rapid and robust assessment of sponge microbial target and
could contribute to deciphering the complexity of these largely unknown host-symbiont interactions. 相似文献
143.
Karen Gilio Matthew T. Harper Judith M. E. M. Cosemans Olga Konopatskaya Imke C. A. Munnix Lenneke Prinzen Michael Leitges Qinghang Liu Jeffery D. Molkentin Johan W. M. Heemskerk Alastair W. Poole 《The Journal of biological chemistry》2010,285(30):23410-23419
Arterial thrombosis, a major cause of myocardial infarction and stroke, is initiated by activation of blood platelets by subendothelial collagen. The protein kinase C (PKC) family centrally regulates platelet activation, and it is becoming clear that the individual PKC isoforms play distinct roles, some of which oppose each other. Here, for the first time, we address all four of the major platelet-expressed PKC isoforms, determining their comparative roles in regulating platelet adhesion to collagen and their subsequent activation under physiological flow conditions. Using mouse gene knock-out and pharmacological approaches in human platelets, we show that collagen-dependent α-granule secretion and thrombus formation are mediated by the conventional PKC isoforms, PKCα and PKCβ, whereas the novel isoform, PKCθ, negatively regulates these events. PKCδ also negatively regulates thrombus formation but not α-granule secretion. In addition, we demonstrate for the first time that individual PKC isoforms differentially regulate platelet calcium signaling and exposure of phosphatidylserine under flow. Although platelet deficient in PKCα or PKCβ showed reduced calcium signaling and phosphatidylserine exposure, these responses were enhanced in the absence of PKCθ. In summary therefore, this direct comparison between individual subtypes of PKC, by standardized methodology under flow conditions, reveals that the four major PKCs expressed in platelets play distinct non-redundant roles, where conventional PKCs promote and novel PKCs inhibit thrombus formation on collagen. 相似文献
144.
Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids 总被引:1,自引:0,他引:1
Mohamed S. Zaibi Jacqueline O’Dowd Mohamed Bellahcene Alastair J.H. Brown Jonathan R.S. Arch 《FEBS letters》2010,584(11):2381-2386
GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Gαi. Here, we agree with a contradictory report in finding no expression of GPR41 in murine adipose tissue. Nevertheless, in the presence of adenosine deaminase to minimise Gαi signalling via the adenosine A1 receptor, SCFA stimulated leptin secretion by adipocytes from wild-type but not GPR41 knockout mice. Expression of GPR43 was reduced in GPR41 knockout mice. Acetate but not butyrate stimulated leptin secretion in wild-type mesenteric adipocytes, consistent with mediation of the response by GPR43 rather than GPR41. Pertussis toxin prevented stimulation of leptin secretion by propionate in epididymal adipocytes, implicating Gαi signalling mediated by GPR43 in SCFA-stimulated leptin secretion. 相似文献
145.
146.
The affinity of a major Ca2+ binding site on GRP78 is differentially enhanced by ADP and ATP 总被引:3,自引:0,他引:3
Lamb HK Mee C Xu W Liu L Blond S Cooper A Charles IG Hawkins AR 《The Journal of biological chemistry》2006,281(13):8796-8805
GRP78 is a major protein regulated by the mammalian endoplasmic reticulum stress response, and up-regulation has been shown to be important in protecting cells from challenge with cytotoxic agents. GRP78 has ATPase activity, acts as a chaperone, and interacts specifically with other proteins, such as caspases, as part of a mechanism regulating apoptosis. GRP78 is also reported to have a possible role as a Ca2+ storage protein. In order to understand the potential biological effects of Ca2+ and ATP/ADP binding on the biology of GRP78, we have determined its ligand binding properties. We show here for the first time that GRP78 can bind Ca2+, ATP, and ADP, each with a 1:1 stoichiometry, and that the binding of cation and nucleotide is cooperative. These observations do not support the hypothesis that GRP78 is a dynamic Ca2+ storage protein. Furthermore, we demonstrate that whereas Mg2+ enhances GRP78 binding to ADP and ATP to the same extent, Ca2+ shows a differential enhancement. In the presence of Ca2+, the KD for ATP is lowered approximately 11-fold, and the KD for ADP is lowered around 930-fold. The KD for Ca2+ is lowered approximately 40-fold in the presence of ATP and around 880-fold with ADP. These findings may explain the biological requirement for a nucleotide exchange factor to remove ADP from GRP78. Taken together, our data suggest that the Ca2+-binding property of GRP78 may be part of a signal transduction pathway that modulates complex interactions between GRP78, ATP/ADP, secretory proteins, and caspases, and this ultimately has important consequences for cell viability. 相似文献
147.
Recently, heterotrophic nanoflagellates (HNF) have been reported to actively ingest prokaryotes in high salinity waters. We report the isolation and culture of an HNF from a Korean saltern pond of 300‰ salinity. The organism is biflagellated with an acronematic anterior flagellum and never glides on surfaces. The mitochondria have tubular cristae. Neither transitional helix nor spiral fiber were observed in the transition zones of the flagella. The cell has a cytostome supported by an arc of eight microtubules, suggesting that our isolate is a bicosoecid. Our isolate had neither mastigonemes, lorica, body scales, nor cytopharynx and thus could not be placed in any of the presently described bicosoecid genera. Phylogenetic analysis of 18S rRNA gene sequences from stramenopiles confirmed the bicosoecid affinities of our isolate, but did not place it within any established genus or family. Its closest relatives include Caecitellus and Cafeteria. The optimal range of growth temperature was 30–35°C. The isolated HNF grew optimally at 150‰ salinity and tolerated up to 363‰ salinity, but it failed to grow below 75‰ salinity, indicating that it could be a borderline extreme halophile. On the basis of its morphological features and position in 18S rRNA trees we propose a novel genus for our isolate; Halocafeteria, n. gen. The species name Halocafeteria seosinensis sp. nov. is proposed. 相似文献
148.
Suemori Y Nagata M Nakamura Y Nakagawa K Okuda A Inagaki J Shinohara K Ogawa M Iida K Dewa T Yamashita K Gardiner A Cogdell RJ Nango M 《Photosynthesis research》2006,90(1):17-21
Light-harvesting antenna core (LH1-RC) complexes isolated from Rhodospirillum rubrum and Rhodopseudomonas palustris were successfully self-assembled on an ITO electrode modified with 3-aminopropyltriethoxysilane. Near infra-red (NIR) absorption,
fluorescence, and IR spectra of these LH1-RC complexes indicated that these LH1-RC complexes on the electrode were stable
on the electrode. An efficient energy transfer and photocurrent responses of these LH1-RC complexes on the electrode were
observed upon illumination of the LH1 complex at 880 nm. 相似文献
149.
Colin E. Adams Deborah J. Hamilton Ian Mccarthy Alastair J. Wilson Alan Grant Gavin Alexander Susan Waldron Sigurdur S. Snorasson Moira M. Ferguson Skuli Skúlason 《Evolutionary ecology》2006,20(1):11-26
There is now increasing acceptance that divergence of phenotypic traits, and the genetic structuring that underlie such divergence, can occur in sympatry. Here we report the serendipitous discovery of a sympatric polymorphism in the upper Forth catchment, Scotland, in a species for which high levels of phenotypic variation have been reported previously, the Arctic charr, Salvelinus alpinus. Attempting to determine the proximate mechanisms through which this pattern of phenotypic variation is maintained, we examine the use of the available feeding resource and the genotypic and phenotypic structure of charr in this system. We show clear differences in head morphology between charr from three very closely connected lakes with no barrier to movement (Lochs Doine, Voil and Lubnaig) and also differences in muscle stable isotope signatures and in stomach contents. There were significant differences at 6 microsatelite loci (between Lubnaig and the other two lochs) and very low estimates of effective migration between populations. We conclude that, despite living in effective sympatry, strong genetic and phenotypic sub-structuring is likely maintained by very high levels of site fidelity, especially during spawning, resulting in functional allopatric divergence of phenotype. 相似文献
150.
In the current study, the improved oral bioavailability of a synthetic astaxanthin derivative (CardaxTM; disodium disuccinate astaxanthin) was utilized to evaluate its potential effects as a cardioprotective agent after 7-day
subchronic oral administration as a feed supplement to Sprague-Dawley rats. Animals received one of two concentrations of
CardaxTM in feed (0.1 and 0.4%; ∼125 and 500 mg/kg/day, respectively) or control feed without drug for 7 days prior to the infarct
study carried out on day 8. Thirty minutes of occlusion of the left anterior descending (LAD) coronary artery was followed
by 2 h of reperfusion prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a percentage (%) of the
area at risk (AAR; IS/AAR,%) of 61 ± 1.8%. The AAR was quantified by Patent blue dye injection, and IS was determined by triphenyltetrazolium
chloride (TTC) staining. CardaxTM at 0.1 and 0.4% in feed for 7 days resulted in a significant mean reduction in IS/AAR,% to 45 ± 2.0% (26% salvage) and 39
± 1.5% (36% salvage), respectively. Myocardial levels of free astaxanthin achieved after 7-day supplementation at each of
the two concentrations (400 ± 65 nM and 1634 ± 90 nM, respectively) demonstrated excellent solid-tissue target organ loading
after oral supplementation. Parallel trends in reduction of plasma levels of multiple lipid peroxidation products with disodium
disuccinate astaxanthin supplementation were observed, consistent with the documented in vitro antioxidant mechanism of action. These results extend the potential utility of this compound for cardioprotection to the
elective human cardiovascular patient population, for which 7-day oral pre-treatment (as with statins) provides significant
reductions in induced periprocedural infarct size. 相似文献