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31.
Xiang L Naik JS Hodnett BL Hester RL 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,290(1):R134-R138
These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 microM SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 microM), arachidonic acid (10 microM), and sodium nitroprusside (0.1, 1, and 10 microM) in the absence or presence of 1 microM SQ-29548. A 10 microM concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 microM SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 microM) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation. 相似文献
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Proteomic identification of glycosylphosphatidylinositol anchor-dependent membrane proteins elevated in breast carcinoma 总被引:1,自引:0,他引:1
Zhao P Nairn AV Hester S Moremen KW O'Regan RM Oprea G Wells L Pierce M Abbott KL 《The Journal of biological chemistry》2012,287(30):25230-25240
The glycosylphosphatidylinositol (GPI) anchor is a lipid and glycan modification added to the C terminus of certain proteins in the endoplasmic reticulum by the activity of a multiple subunit enzyme complex known as the GPI transamidase (GPIT). Several subunits of GPIT have increased expression levels in breast carcinoma. In an effort to identify GPI-anchored proteins and understand the possible role of these proteins in breast cancer progression, we employed a combination of strategies. First, alpha toxin from Clostridium septicum was used to capture GPI-anchored proteins from human breast cancer tissues, cells, and serum for proteomic analysis. We also expressed short interfering RNAs targeting the expression of the GPAA1 and PIGT subunits of GPIT in breast cancer cell lines to identify proteins in which membrane localization is dependent on GPI anchor addition. Comparative membrane proteomics using nano-ESI-RPLC-MS/MS led to the discovery of several new potential diagnostic and therapeutic targets for breast cancer. Furthermore, we provide evidence that increased levels of GPI anchor addition in malignant breast epithelial cells promotes the dedifferentiation of malignant breast epithelial cells in part by increasing the levels of cell surface markers associated with mesenchymal stem cells. 相似文献
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Laura S. Weyrich Olivier Y. Rolin Sarah J. Muse Jihye Park Nicholas Spidale Mary J. Kennett Sara E. Hester Chun Chen Edward G. Dudley Eric T. Harvill 《PloS one》2012,7(10)
Type VI Secretion Systems (T6SSs) have been identified in numerous Gram-negative pathogens, but the lack of a natural host infection model has limited analysis of T6SS contributions to infection and pathogenesis. Here, we describe disruption of a gene within locus encoding a putative T6SS in Bordetella bronchiseptica strain RB50, a respiratory pathogen that circulates in a broad range of mammals, including humans, domestic animals, and mice. The 26 gene locus encoding the B. bronchiseptica T6SS contains apparent orthologs to all known core genes and possesses thirteen novel genes. By generating an in frame deletion of clpV, which encodes a putative ATPase required for some T6SS-dependent protein secretion, we observe that ClpV contributes to in vitro macrophage cytotoxicity while inducing several eukaryotic proteins associated with apoptosis. Additionally, ClpV is required for induction of IL-1β, IL-6, IL-17, and IL-10 production in J774 macrophages infected with RB50. During infections in wild type mice, we determined that ClpV contributes to altered cytokine production, increased pathology, delayed lower respiratory tract clearance, and long term nasal cavity persistence. Together, these results reveal a natural host infection system in which to interrogate T6SS contributions to immunomodulation and pathogenesis. 相似文献
36.
Xiang L Dearman J Abram SR Carter C Hester RL 《American journal of physiology. Heart and circulatory physiology》2008,294(4):H1658-H1666
Individuals with metabolic syndrome exhibit insulin resistance and an attenuated functional vasodilatory response to exercise. We have shown that impaired functional vasodilation in obese Zucker rats (OZRs) is associated with enhanced thromboxane receptor (TP)-mediated vasoconstriction. We hypothesized that insulin resistance, hyperglycemia/hyperlipidemia, and the resultant ROS are responsible for the increased TP-mediated vasoconstriction in OZRs, resulting in impaired functional vasodilation. Eleven-week-old male lean Zucker rats (LZRs) and OZRs were fed normal rat chow or chow containing rosiglitazone (5 mg.kg(-1).day(-1)) for 2 wk. In another set of experiment, LZRs and OZRs were treated with 2 mM tempol (drinking water) for 7-10 days. After the treatments, spinotrapezius muscles were prepared, and arcade arteriolar diameters were measured following muscle stimulation and arachidonic acid (AA) application (10 muM) in the absence and presence of the TP antagonist SQ-29548 (1 muM). OZRs exhibited higher insulin, glucose, triglyceride, and superoxide levels and increased NADPH oxidase activity compared with LZRs. Functional and AA-induced vasodilations were impaired in OZRs. Rosiglitazone treatment improved insulin, glucose, triglyceride, and superoxide levels as well as NADHP oxidase activity in OZRs. Both rosiglitazone and tempol treatment improved vasodilatory responses in OZRs with no effect in LZRs. SQ-29548 treatment improved vasodilatory responses in nontreated OZRs with no effect in LZRs or treated OZRs. These results suggest that insulin resistance and the resultant increased ROS impair functional dilation in OZRs by increasing TP-mediated vasoconstriction. 相似文献
37.
The purpose of this study was to determine how diverse momentum conditions and anatomical orientation at contact influences mechanical loading and multijoint control of the reaction force during landings. Male collegiate gymnasts (n=6) performed competition style landings (n=3) of drop jumps, front saltos, and back saltos from a platform (0.72 m) onto landing mats (0.12 m). Kinematics (200 fps), reaction forces (800 Hz) and muscle activation patterns (surface EMG, 1600 Hz) of seven lower extremity muscles were collected simultaneously. Between-task differences in segment orientation relative to the reaction force contributed to significant between-task differences in knee and hip net joint moments (NJM) during the impact phase. During the stabilization phase, ankle, knee, and hip NJMs acted to control joint flexion. Between-task differences in muscle activation patterns indicated that gymnasts scaled biarticular muscle activation to accommodate for between-task differences in NJM after contact. Activation of muscles on both sides of the joint suggests that impedance like control was used to stabilize the joints and satisfy the mechanical demand imposed on the lower extremity. Between-subject differences in the set of muscles used to control total body center of mass (TBCM) trajectory and achieve lower extremity NJMs suggests that control of multijoint movements involving impact needs to incorporate mechanical objectives at both the total body and local level. The functional consequences of such a control structure may prove to be an asset to gymnasts, particularly when required to perform a variety of landing tasks under a variety of environmental constraints. 相似文献
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The detectability of invasive organisms influences the costs and benefits of alternative control strategies, and the feasibility of eradicating an infestation. Search theory offers a mathematically rigorous framework for defining and measuring detectability taking account of searcher ability, biological factors and the search environment. In this paper, invasive species detectability is incorporated into a population simulation model. The model is applied to a base set of parameter values that represent reasonable values for a hypothetical weed. The analysis shows the effects of detectability and search effort on the duration of an eradication program. For a given level of detectability and search time, the analysis shows that the variables with the greatest influence on the duration of the eradication effort are search speed, kill efficiency, germination rate and seed longevity. Monte Carlo simulations are performed on a set of four weed scenarios, involving different combinations of plant longevity, seed longevity and plant fecundity. Results of these simulations are presented as probability distributions and allow us to calculate how the probability of eradication will be affected by search strategy. 相似文献
40.
Activity patterns and resource use by sheep and red deer grazing across a grass/heather boundary 总被引:2,自引:0,他引:2
Diet selection and activities of sheep and red deer grazing alone and together across a grass (primarily Lolium perenne/Agrostis capillaris ) and heather ( Calluna vulgaris ) boundary, between July and October, are described.
Throughout the experiment, both animal species had a much higher proportion of grass than heather in their diet. Time spent grazing on each type of vegetation was similarly greater on grass, and the bite rates of the animals were also more rapid on the grass than on the heather.
Red deer spent more time grazing per 24 hours than did sheep, with sheep grazing less during darkness hours than red deer. Total grazing time of both species did not decrease with decreasing daylength from July to October.
There were no consistent differences in the diurnal patterns of activity of sheep and red deer, with both species showing 2-3 large grazing peaks per day.
There were no consistent effects of mixing sheep and deer on their grazing behaviour and diet composition. 相似文献
Throughout the experiment, both animal species had a much higher proportion of grass than heather in their diet. Time spent grazing on each type of vegetation was similarly greater on grass, and the bite rates of the animals were also more rapid on the grass than on the heather.
Red deer spent more time grazing per 24 hours than did sheep, with sheep grazing less during darkness hours than red deer. Total grazing time of both species did not decrease with decreasing daylength from July to October.
There were no consistent differences in the diurnal patterns of activity of sheep and red deer, with both species showing 2-3 large grazing peaks per day.
There were no consistent effects of mixing sheep and deer on their grazing behaviour and diet composition. 相似文献