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21.
Wang Y Ho G Zhang JJ Nieuwenhuijsen B Edris W Chanda PK Young KH 《The Journal of biological chemistry》2002,277(50):48325-48332
Regulator of G protein signaling (RGS) proteins constitute a family of over 20 proteins that negatively regulate heterotrimeric G protein-coupled receptor signaling pathways by enhancing endogenous GTPase activities of G protein alpha subunits. RGSZ1, one of the RGS proteins specifically localized to the brain, has been cloned previously and described as a selective GTPase accelerating protein for Galpha(z) subunit. Here, we employed several methods to provide new evidence that RGSZ1 interacts not only with Galpha(z,) but also with Galpha(i), as supported by in vitro binding assays and functional studies. Using glutathione S-transferase fusion protein pull-down assays, glutathione S-transferase-RGSZ1 protein was shown to bind (35)S-labeled Galpha(i1) protein in an AlF(4)(-)dependent manner. The interaction between RGSZ1 and Galpha(i) was confirmed further by co-immunoprecipitation studies and yeast two-hybrid experiments using a quantitative luciferase reporter gene. Extending these observations to functional studies, RGSZ1 accelerated endogenous GTPase activity of Galpha(i1) in single-turnover GTPase assays. Human RGSZ1 functionally regulated GPA1 (a yeast Galpha(i)-like protein)-mediated yeast pheromone response when expressed in a SST2 (yeast RGS protein) knockout strain. In PC12 cells, transfected RGSZ1 blocked mitogen-activated protein kinase activity induced by UK14304, an alpha(2)-adrenergic receptor agonist. Furthermore, RGSZ1 attenuated D2 dopamine receptor agonist-induced serum response element reporter gene activity in Chinese hamster ovary cells. In summary, these data suggest that RGSZ1 serves as a GTPase accelerating protein for Galpha(i) and regulates Galpha(i)-mediated signaling, thus expanding the potential role of RGSZ1 in G protein-mediated cellular activities. 相似文献
22.
Within-cluster resampling 总被引:1,自引:0,他引:1
23.
Gregory J. Tanner Michelle L. Colgrave Malcolm J. Blundell Hareshwar P. Goswami Crispin A. Howitt 《PloS one》2013,8(2)
Background
Subjects suffering from coeliac disease, gluten allergy/intolerance must adopt a lifelong avoidance of gluten. Beer contains trace levels of hordeins (gluten) which are too high to be safely consumed by most coeliacs. Accurate measurement of trace hordeins by ELISA is problematic.Methods
We have compared hordein levels in sixty beers, by sandwich ELISA, with the level determined using multiple reaction monitoring mass spectrometry (MRM-MS).Results
Hordein levels measured by ELISA varied by four orders of magnitude, from zero (for known gluten-free beers) to 47,000 µg/mL (ppm; for a wheat-based beer). Half the commercial gluten-free beers were free of hordein by MS and ELISA. Two gluten-free and two low-gluten beers had zero ELISA readings, but contained significant hordein levels (p<0.05), or near average (60–140%) hordein levels, by MS, respectively. Six beers gave false negatives, with zero ELISA readings but near average hordein content by MS. Approximately 20% of commercial beers had ELISA readings less than 1 ppm, but a near average hordein content by MS. Several barley beers also contained undeclared wheat proteins.Conclusions
ELISA results did not correlate with the relative content of hordein peptides determined by MS, with all barley based beers containing hordein. We suggest that mass spectrometry is more reliable than ELISA, as ELISA enumerates only the concentration of particular amino-acid epitopes; this may vary between different hordeins and may not be related to the absolute hordein concentration. MS quantification is undertaken using peptides that are specific and unique, enabling the quantification of individual hordein isoforms. This outlines the problem of relying solely on ELISA determination of gluten in beverages such as beer and highlights the need for the development of new sensitive and selective quantitative assay such as MS. 相似文献24.
Pradyot Bhattacharya Smriti Ghosh Sarfaraz Ahmad Ejazi Mehebubar Rahaman Krishna Pandey Vidya Nand Ravi Das Pradeep Das Rama Prosad Goswami Bibhuti Saha Nahid Ali 《PLoS neglected tropical diseases》2016,10(2)
Background
Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown.Methodology/Principal Findings
We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFβ and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFβ and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFβ to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFβ respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFβ in comparison to corresponding CD25- T cells.Conclusions/Significance
Our findings shed some light on source(s) of TGFβ and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4+CD25+FoxP3+ Treg cells as a source of IL-10 and TGFβ during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease. 相似文献25.
26.
On binding toVicia faba lectin, the fluorescence of 4-methylumbelliferyl-α-D-glucoPyranoside was quantitatively quenched showing that the interaction
of 4-methylumbelliferyl-α-D-glucoPyranoside took Place in a binding environment. The binding of the fluorescent sugar was
saccharide sPecific as evidenced by the reversal of 4-methylumbelliferyl-α-D-glucoPyranoside fluorescence quenching by D-fructose.
The association constant,K
a, values for the 4-methylumbelliferyl-α-D-glucoPyranoside was determined by comPetition study emPloying reversal of fluorescence
quenching of 4-methylumbelliferyl-α-D-glucoPyranoside by D-fructose. TheK
a value obtained for D-fructose was 1.07 ±0.03 X 104 M-1 and for 4-methylumbelliferyl-α-D-glucoPyranoside was 1.60 ±0.05 X 104 M-1 at 15°C. TheK
a values of 2.51 ±0.06 X 104M-1, l.26 ±0.02 X 104 M-1 and 0.56 ±0.01 X 104M-1, resPectively at 10°, 20° and 30°C were obtained from the ChiPman equation. The relative fluorescence quenching, ΔF
a, at infinite concentration of the free saccharide sites ofVicia faba lectin [P′] was 93.5% at 30°C and the binding constant for 4-methylumbelliferyl-α-D-glucoPyranoside lectin interaction as derived by
Yank and Hanaguchi equation was 0.63 ±0.01 X 104M-1. 相似文献
27.
Pollen of pigeonpea(Cajanus cajan (L.) Millsp.) cultivars H-77-216 and ICPL-151 were cultivatedin vitro at six different temperatures (12, 17, 22, 27, 32, 37 °C). Pollen of cv. H-77-216 started to germinate at 17 °C whereas the pollen of cv. ICPL-151 at 22 °C, the optimal temperatures were 22 and 27 °C, respectively. Pollen germination at different temperatures was found to be positively correlated with the tube length. Per cent pollen bursting increased with rising temperature. The indeterminate cv. H-77-216 showed a wide range of suitable temperatures (17 – 27 °C) for pollen germination while the determinate cv. ICPL-151 had optimum at 27 °C 相似文献
28.
Background
Which factors influence the distribution patterns of morphological diversity among clades? The adaptive radiation model predicts that a clade entering new ecological niche will experience high rates of evolution early in its history, followed by a gradual slowing. Here we measure disparity and rates of evolution in Carnivora, specifically focusing on the terrestrial-aquatic transition in Pinnipedia. We analyze fissiped (mostly terrestrial, arboreal, and semi-arboreal, but also including the semi-aquatic otter) and pinniped (secondarily aquatic) carnivorans as a case study of an extreme ecological transition. We used 3D geometric morphometrics to quantify cranial shape in 151 carnivoran specimens (64 fissiped, 87 pinniped) and five exceptionally-preserved fossil pinnipeds, including the stem-pinniped Enaliarctos emlongi. Range-based and variance-based disparity measures were compared between pinnipeds and fissipeds. To distinguish between evolutionary modes, a Brownian motion model was compared to selective regime shifts associated with the terrestrial-aquatic transition and at the base of Pinnipedia. Further, evolutionary patterns were estimated on individual branches using both Ornstein-Uhlenbeck and Independent Evolution models, to examine the origin of pinniped diversity.Results
Pinnipeds exhibit greater cranial disparity than fissipeds, even though they are less taxonomically diverse and, as a clade nested within fissipeds, phylogenetically younger. Despite this, there is no increase in the rate of morphological evolution at the base of Pinnipedia, as would be predicted by an adaptive radiation model, and a Brownian motion model of evolution is supported. Instead basal pinnipeds populated new areas of morphospace via low to moderate rates of evolution in new directions, followed by later bursts within the crown-group, potentially associated with ecological diversification within the marine realm.Conclusion
The transition to an aquatic habitat in carnivorans resulted in a shift in cranial morphology without an increase in rate in the stem lineage, contra to the adaptive radiation model. Instead these data suggest a release from evolutionary constraint model, followed by aquatic diversifications within crown families.Electronic supplementary material
The online version of this article (doi:10.1186/s12862-015-0285-5) contains supplementary material, which is available to authorized users. 相似文献29.
Greater female autonomy is mirrored through better performance in the major demographic and social indicators. This study attempts to capture the effect of religion on the status of women considering 'Greater Bengal'. There is much evidence suggesting that when cultural factors are constant, religion does not have a significant effect on any demographic issue. In this paper, the validity of this proposition is examined using two datasets, namely NFHS II (98-99) and BDHS 2000. It is clear from the analyses that not only region but also religion has a distinct effect on the status of women. In West Bengal, the religious gap for all the indicators considered is pretty high, whereas in Bangladesh the gap is not that wide. A state-level population policy is needed in West Bengal to act as a social leveller. 相似文献
30.
Curcumin is a natural polyphenolic compound having an antiproliferative property, which recent evidence suggests is due to its ability to induce apoptosis. However, the molecular mechanisms through which curcumin induces apoptosis are not fully understood. Here, we report that the curcumin-induced apoptosis is mediated through the impairment of the ubiquitin-proteasome system. Exposure of curcumin to the mouse neuro 2a cells causes a dose-dependent decrease in proteasome activity and an increase in ubiquitinated proteins. Curcumin exposure also decreases the turnover of the destabilized enhanced green fluorescence protein, a model substrate for proteasome and cellular p53 protein. Like other proteasome inhibitors, curcumin targets proliferative cells more efficiently than differentiated cells and induces apoptosis via mitochondrial pathways. Addition of curcumin to neuro 2a cells induces a rapid decrease in mitochondrial membrane potential and the release of cytochrome c into cytosol, followed by activation of caspase-9 and caspase-3. 相似文献