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11.
The factors that determine why ecosystems exhibit abrupt shifts in state are of paramount importance for management, conservation, and restoration efforts. Kelp forests are emblematic of such abruptly shifting ecosystems, transitioning from kelp-dominated to urchin-dominated states around the world with increasing frequency, yet the underlying processes and mechanisms that control their dynamics remain unclear. Here, we analyze four decades of data from biannual monitoring around San Nicolas Island, CA, to show that substrate complexity controls both the number of possible (alternative) states and the velocity with which shifts between states occur. The superposition of community dynamics with reconstructions of system stability landscapes reveals that shifts between alternative states at low-complexity sites reflect abrupt, high-velocity events initiated by pulse perturbations that rapidly propel species across dynamically unstable state–space. In contrast, high-complexity sites exhibit a single state of resilient kelp–urchin coexistence. Our analyses suggest that substrate complexity influences both top-down and bottom-up regulatory processes in kelp forests, highlight its influence on kelp-forest stability at both large (island-wide) and small (<10 m) spatial scales, and could be valuable for holistic kelp-forest management.

Kelp-forest ecosystems exhibit rich and varied spatiotemporal dynamics. Prominent among these are dramatic shifts between kelp-dominated forests and so-called urchin barrens from which macroalgae are almost entirely absent due to intense urchin grazing (1, 2). Phase shifts between kelp and barren states have long been associated with structural changes to kelp-forest communities, such as the addition or removal of sea-urchin predators (3, 4) or changes in the environment such as shifting water temperatures (47). Kelp forests are also subject to stochastic perturbations such as large wave, marine disease, and anomalous warm water events that might perturb kelp forests between alternative stable states (8, 9). However, distinguishing phase shifts and alternative stable states is a major challenge (10). This is partially because both slow environmental change and relatively rapid stochastic perturbations often appear to act synergistically and with episodic urchin recruitment events that, due to their large regional extent, decouple rates of urchin grazing from the local density-dependent regulation of their populations (11, 12).Although consensus is emerging that the maintenance of kelp-dominated forests is driven by a combination of top-down and bottom-up processes, the mechanisms underlying these processes—and hence the optimal means to control and avoid tipping points to the urchin-barren state—appear varied and often unclear (1, 13). For example, top-down processes contributing to kelp-forest stability include the effects of predators and disease on urchin grazing behavior and mortality rates (1418), emphasizing the need for management strategies that preserve or restore top-down forms of urchin control (19, 20). On the other hand, bottom-up processes affecting kelp growth and senescence rates, and the retention of drift algae that urchins prefer to consume, are also known to contribute to kelp-forest stability, emphasizing management strategies that differ from those of direct urchin control (2125). We hypothesize that substrate complexity modifies both top-down and bottom-up processes structuring urchin–kelp interactions, e.g., provisioning habitat for urchin predators and increasing the retention of drift algae for urchins.Here we apply the perspective of stochastic dynamical systems to the study of kelp forests not to determine the specific mechanisms or feedbacks that underlie kelp-forest dynamics but rather to infer an environmental variable that influences their relative strength and net expression. The dynamical-systems perspective conceptualizes a system’s community states and dynamics using the ball-in-cup heuristic of stability and resilience (26, 27), formally described by a (quasi-)potential stability landscape (28, 29). A system with alternative stable states exhibits a multimodal landscape with two or more basins of attraction (cups) over which it travels in time due to endogenous drivers (e.g., species interactions) and external perturbations. Because most perturbations are directionally random and small, communities spend more time in states at the bottom of the attracting basins than they do on their slopes and cusps, with deeper and steeper-sloped basins corresponding to more stable and resilient community states whose dynamics are dominated by negative feedbacks (28). Previous work has utilized this characteristic of stochastic dynamical systems to make use of large-scale spatial variation in community structure to infer what biotic and environmental conditions may alter the stability of various ecological systems, including tropical and temperate forests and desert biomes (4, 3032). For example, Scheffer et al. (33) used satellite-derived spatial variation in the frequency distributions of percentage of tree cover values to infer that boreal biomes exhibit between one and three different alternative stable states whose number and nature depend on mean July temperature, where empirical system–state frequency histograms represent negative potential (i.e., a mirror image of a ball-in-cup stability landscape reflected across the x axis). Similarly, Ling et al. (4) combined spatial survey data with translocation experiments to infer bistability in response to urchin densities in Tasmanian kelp forests. The approach underlying these inferences has been referred to as potential analysis (34).Using spatially fixed and replicated long-term time series of kelp-forest community dynamics around San Nicolas Island, CA, we extended the application of potential analysis to include the temporal domain to more rigorously infer their condition-dependent stability landscapes and shifts in community structure. Our analyses reveal kelp-forest communities around San Nicolas Island to exhibit dramatic, perturbation-induced shifts between kelp-dominated forests and urchin-barren states only when the complexity of the underlying substrate is low and that similarly perturbed high-complexity substrates permit only a single persistent state of resilient kelp–urchin coexistence. We infer that substrate complexity at San Nicolas Island controls the relative strength of the many negative and positive feedbacks that have been described in kelp forests and that a greater understanding of its influences is likely to increase the effectiveness of management efforts seeking to conserve and restore their existence.  相似文献   
12.
Non-neuronal cells may be pivotal in neurodegenerative disease, but the mechanistic basis of this effect remains ill-defined. In the polyglutamine disease spinocerebellar ataxia type 7 (SCA7), Purkinje cells undergo non-cell-autonomous degeneration in transgenic mice. We considered the possibility that glial dysfunction leads to Purkinje cell degeneration, and generated mice that express ataxin-7 in Bergmann glia of the cerebellum with the Gfa2 promoter. Bergmann glia-specific expression of mutant ataxin-7 was sufficient to produce ataxia and neurodegeneration. Expression of the Bergmann glia-specific glutamate transporter GLAST was reduced in Gfa2-SCA7 mice and was associated with impaired glutamate transport in cultured Bergmann glia, cerebellar slices and cerebellar synaptosomes. Ultrastructural analysis of Purkinje cells revealed findings of dark cell degeneration consistent with excitotoxic injury. Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs.  相似文献   
13.

BACKGROUND:

The Canadian guidelines recommend blood glucose (BG) screening starting at 2 h of age in asymptomatic ‘at-risk’ babies (including small-for-gestational-age [SGA] and large-for-gestational-age [LGA] infants), with intervention cut-offs of 1.8 mmol/L and 2.6 mmol/L. The present study reviews and audits this practice in full-term newborn populations.

METHODS:

A literature review meta-analyzed BG values in appropriate-for-gestational age (AGA) term newborns to establish normal 1 h, 2 h and 3 h values. A clinical review audited screening of ‘at-risk’ SGA and LGA term newborns, evaluating both clinical burden and validity.

RESULTS:

The review included six studies, although none clearly defined the plasma glucose standard. The pooled mean (plasma) BG level in AGA babies 2 h of age was 3.35 mmol/L (SD=0.77), significantly higher than 1 h levels (3.01 mmol/L, SD=0.96). In the audit, 78 SGA and 142 LGA babies each had an average of 6.0 and 4.7 BG tests, respectively. The mean 2 h BG levels for SGA (3.42 mmol/L, SD=1.02) and LGA (3.31 mmol/L, SD=0.66) babies did not differ significantly from the AGA pooled mean. Receiver operating characteristic curves showed that 2 h BG levels in LGA and SGA babies predicted later hypoglycemia (defined as a BG level lower than 2.6 mmol/L), but sensitivities and specificities were poor.

CONCLUSIONS:

Published 2 h BG levels for AGA babies are higher than 1 h values and are similar to audited 2 h levels in SGA and LGA babies. Clinically, 2 h levels are predictive of later hypoglycemia but may require repeat BG testing. Audit is an important tool to validate national guidelines, to minimize their burden and to maximize their utility.  相似文献   
14.
15.

Background

Robust methods to culture primary airway epithelial cells were developed several decades ago and these cells provide the model of choice to investigate many diseases of the human lung. However, the molecular signature of cells from different regions of the airway epithelium has not been well characterized.

Methods

We utilize DNase-seq and RNA-seq to examine the molecular signatures of primary cells derived from human tracheal and bronchial tissues, as well as healthy and diseased (cystic fibrosis (CF)) donor lung tissue.

Results

Our data reveal an airway cell signature that is divergent from other epithelial cell types and from common airway epithelial cell lines. The differences between tracheal and bronchial cells are clearly evident as are common regulatory features. Only minor variation is seen between bronchial cells from healthy or CF donors.

Conclusions

These data are a valuable resource for functional genomics analysis of airway epithelial tissues in human disease.  相似文献   
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This randomised, double-blind, double-dummy, cumulative dose, multicentre crossover study aimed to demonstrate non-inferiority in safety of formoterol delivered via Easyhaler versus Aerolizer. The secondary objective was to compare the efficacy of the devices. Thirty-three adult asthmatic subjects entered the study and 32 completed it. The study comprised screening and two study days, with each subject inhaling 96 microg (12, 12, 24 and 48 microg) cumulative dose of formoterol via the study inhalers. Serum potassium (S-K+), vital signs and spirometry were performed at baseline, 1h after each dose and additionally 4h after the last dose. The primary safety variable was S-K+. Secondary safety variables were heart rate, corrected QT interval, blood pressure, serum glucose and adverse events. Spirometry was assessed to evaluate efficacy. The results showed non-inferiority in safety of formoterol inhaled via Easyhaler compared to Aerolizer. The adjusted treatment difference in the S-K+ values after 96 microg cumulative dose of formoterol was 0.14 mmol/L being clearly above the pre-determined lower limit of the non-inferiority criterion of -0.2 mmol/L. There were dose-related changes in secondary efficacy variables after both treatments. The changes were comparable in most of the parameters but heart rate was statistically significantly higher and decrease in diastolic blood pressure greater after formoterol via Aerolizer than that via Easyhaler. The occurrence of adverse events was dose-related, the most common events being tremor, hypokalaemia, headache and palpitation. The spirometry results showed no statistically significant difference in efficacy between the treatments. In conclusion, formoterol delivered via Easyhaler was as safe as via Aerolizer.  相似文献   
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