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981.
Understanding variability in patterns of parasite infections requires studies of multiple populations inhabiting a variety of habitats. Gastrointestinal parasites of chimpanzees (Pan troglodytes) have been studied extensively at several forested sites, but the parasite fauna of chimpanzees living in dry, open habitats is less well known. We studied the parasites of savanna chimpanzees (Pan troglodytes schweinfurthii) living in the Issa Valley, Ugalla (Tanzania). We examined 119 fresh fecal samples using standard coproscopical methods. We detected protozoans including Blastocystis sp., Entamoeba coli, E. histolytica/dispar, Iodamoeba buetschlii, Troglodytella abrassarti, and Troglocorys cava, but only two types of spirurid nematodes among the helminths. The parasites of the Ugalla chimpanzees differ from those of forest chimpanzees in the absence of Strongyloides sp. and strongylid nematodes and a high prevalence of spirurids. Strongylids and Strongyloides sp. have thin-shelled eggs and larvae, which develop in the external environment; thus they may not be able to survive for prolonged periods in the extreme environment of Ugalla. The Ugalla chimpanzees also live at a lower population density and exhibit a larger home range than forest chimpanzees, factors that may lead to lower exposure to infective nematode larvae. Spirurid eggs, however, have thick shells and a life cycle dependent on intermediary hosts, making their survival and transmission in such extreme conditions more feasible. These differences between parasite fauna of closed and open forest chimpanzees contribute to our understanding of the ecology of infectious disease, and have the potential to contribute to conservation policies and practices.  相似文献   
982.

Background

Reactive oxygen species-mediated cysteine sulfenic acid modification has emerged as an important regulatory mechanism in cell signaling. The stability of sulfenic acid in proteins is dictated by the local microenvironment and ability of antioxidants to reduce this modification. Several techniques for detecting this cysteine modification have been developed, including direct and in situ methods.

Scope of review

This review presents a historical discussion of sulfenic acid chemistry and highlights key examples of this modification in proteins. A comprehensive survey of available detection techniques with advantages and limitations is discussed. Finally, issues pertaining to rates of sulfenic acid formation, reduction, and chemical trapping methods are also covered.

Major conclusions

Early chemical models of sulfenic acid yielded important insights into the unique reactivity of this species. Subsequent pioneering studies led to the characterization of sulfenic acid formation in proteins. In parallel, the discovery of oxidant-mediated cell signaling pathways and pathological oxidative stress has led to significant interest in methods to detect these modifications. Advanced methods allow for direct chemical trapping of protein sulfenic acids directly in cells and tissues. At the same time, many sulfenic acids are short-lived and the reactivity of current probes must be improved to sample these species, while at the same time, preserving their chemical selectivity. Inhibitors with binding scaffolds can be rationally designed to target sulfenic acid modifications in specific proteins.

General significance

Ever increasing roles for protein sulfenic acids have been uncovered in physiology and pathology. A more complete understanding of sulfenic acid-mediated regulatory mechanisms will continue to require rigorous and new chemical insights. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.  相似文献   
983.

Background

The NLRP3 inflammasome is a sensor of specific pathogen, host and environmental danger molecules. Upon activation NLRP3 recruits caspase-1, which cleaves and thereby activates precursor interleukin-1β (IL-1β) and IL-18 to initiate immune responses. Several recent studies have posited that the mitochondria are a central regulator of NLRP3 function.

Scope of review

Mitochondrial reactive oxygen species (mtROS) production, mitochondrial apoptosis, mitochondrial DNA (mtDNA) release, mitophagy, calcium induced mitochondrial damage and mitochondrial co-ordination of NLRP3 localization have all been implicated in regulating NLRP3 activity. In this article we review the literature both for and against these models of NLRP3 inflammasome activation, and highlight other recent contentious issues concerning NLRP3 functioning.

Major conclusions

Although many mechanisms have been proposed for activating NLRP3, no unified model has yet to gain acceptance. Further research is required to clarify how the mitochondria might influence NLRP3 activity.

General significance

While the NLRP3 inflammasome is important for host protection against microbial infection, rare genetic mutations in NLRP3 also cause severe auto-inflammatory diseases. More recent research has implicated NLRP3 activity in pathologies such as atherosclerosis, cancer, type 2 diabetes and Alzheimer's disease. Understanding the mechanisms of NLRP3 inflammasome formation and regulation therefore has the potential to uncover new inflammasome and disease specific therapeutic targets. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.  相似文献   
984.
Understanding how climate change can affect crop‐pollinator systems helps predict potential geographical mismatches between a crop and its pollinators, and therefore identify areas vulnerable to loss of pollination services. We examined the distribution of orchard species (apples, pears, plums and other top fruits) and their pollinators in Great Britain, for present and future climatic conditions projected for 2050 under the SRES A1B Emissions Scenario. We used a relative index of pollinator availability as a proxy for pollination service. At present, there is a large spatial overlap between orchards and their pollinators, but predictions for 2050 revealed that the most suitable areas for orchards corresponded to low pollinator availability. However, we found that pollinator availability may persist in areas currently used for fruit production, which are predicted to provide suboptimal environmental suitability for orchard species in the future. Our results may be used to identify mitigation options to safeguard orchard production against the risk of pollination failure in Great Britain over the next 50 years; for instance, choosing fruit tree varieties that are adapted to future climatic conditions, or boosting wild pollinators through improving landscape resources. Our approach can be readily applied to other regions and crop systems, and expanded to include different climatic scenarios.  相似文献   
985.

Background

The IL-1 family of cytokines is known to play an important role in inflammation therefore understanding the mechanism by which they are produced is paramount. Despite the recent plethora of publications dedicated to the study of these cytokines, the mechanism by which they are produced in the airway following endotoxin, Lipopolysaccharide (LPS), exposure is currently unclear. The aim was to determine the mechanism by which the IL-1 cytokines are produced after LPS inhaled challenge.

Methods

Mice were challenged with aerosolised LPS, and lung tissue and bronchiolar lavage fluid (BALF) collected. Targets were measured at the mRNA and protein level; caspase activity was determined using specific assays.

Results

BALF IL-1b/IL-18, but not IL-1a, was dependent on Ice Protease-Activating Factor (IPAF), and to a lesser extent Apoptosis-associated Speck-like protein containing a CARD (ASC). Interestingly, although we measured an increase in mRNA expression for caspase 1 and 11, we could not detect an increase in lung enzyme activity or a role for them in IL-1a/b production. Further investigations showed that whilst we could detect an increase in caspase 8 activity at later points in the time course (during resolution of inflammation), it appeared to play no role in the production of IL-1 cytokines in this model system.

Conclusions

TLR4 activation increases levels of BALF IL-1b/IL-18 via an IPAF dependent and caspase 1/11/8 independent pathway. Furthermore, it would appear that the presence of IL-1a in the BALF is independent of these pathways. This novel data sheds light on innate signalling pathways in the lung that control the production of these key inflammatory cytokines.  相似文献   
986.
Understanding the behavior of laboratory NHP facilitates health assessment and clinical care. We sought to characterize the behavior of critically ill rhesus macaques (Macaca mulatta) and determine whether specific behaviors or behavioral changes might facilitate the determination of prognosis and clinical endpoints. Twenty-two critically-ill subjects were videorecorded after they were removed from the outdoor breeding colony for diagnostic work-up and treatment. Subjects were categorized as survivors (n = 15) and those that were euthanized according to existing clinical endpoints (n = 7). Behavior before, during, and after cageside examination was compared between these groups with regard to the presence or absence of direct observation. This approach allowed us to determine whether these settings revealed differences between groups or masking of behaviors during direct observation. Before cageside examination, several behaviors (for example, self-grooming and anxiety behaviors) were significantly more common in surviving subjects than in euthanized subjects. Few significant differences in behavior were detectable during or after the examination. Subjects that were eventually euthanized showed more illness-related behaviors; however, not all animals requiring euthanasia showed these signs when an observer was present. Furthermore, euthanized animals spent more time in an alert posture during direct observation than at other times. Therefore, direct observation of critically ill rhesus macaques may not yield the most accurate assessment of illness severity, and using video to assess behavior may be helpful for prognosis.The assessment and recognition of pain and distress in laboratory animals is crucial to ensure welfare and high-quality research.6,10,12,20,23,26,28 Difficulty in identifying species-specific signs of pain and distress suggests that cageside assessment of clinical condition by an observer, as a stand-alone method, may not be an optimal method of determining prognosis in critically ill animals of some species.10,24,26,27 The behavior of NHP, including rhesus macaques (Macaca mulatta), can be especially difficult to interpret due to their relatively stoic nature and tendency to mask clinical signs of illness in the presence of human observers.8,10,12,14,17 Two explanations for the tendency to mask pain, which is also observed in other species, are their status as a prey species and the need to hide weaknesses from group members.3,17,22,23 According to the 2009 Institute for Laboratory Animal Research (ILAR) recommendations for recognizing pain and distress in nonhuman primates, “[v]iewing an animal from a distance or by video can aid in detecting subtle clinical changes.”12 The goal of the current study was to evaluate the use of videotaped behavioral data to increase accuracy in predicting prognoses for rhesus macaques that are critically ill.A humane endpoint is defined as the earliest time at which an animal may experience unnecessary pain or distress, undue suffering, or impending death.4,12 Both subjective and objective diagnostic criteria are currently used to define clinical and research endpoints.6,7,10,12,21,26,29A myriad of diagnostics can be used for this purpose, including physical examination, cageside examination, blood assays (CBC and serum biochemistry), imaging (radiographs, ultrasound, CT, and MRI), bacterial culture and sensitivity, urinalysis, and collection of tissue samples (fine-needle aspiration and biopsy). One specific example of using clinical diagnostics to aid in the prediction of mortality in NHP involved using acid-base levels in animals with severe social trauma.11 Behavioral assessment may be an important and underutilized diagnostic method for assessing pain and distress. Recent studies have evaluated the behavior, specifically facial expression, of mice to detect and assess pain.16,19 Methods for evaluating behavior typically involve cageside examination, but assessment of behavior via videotape in the absence of an observer may also be useful.Endpoints may vary depending on species, nature of the research conducted, and assessment of degree of pain or distress. At our facility, experimental endpoints (those defined as part of a specific study) are differentiated from clinical endpoints (those determined by an animal''s health and quality of life). The veterinarian has the authority to elect euthanasia for an animal that is assessed to have reached an endpoint by either or both classifications. IACUC-approved endpoint policies have been established to aid in this decision. Criteria included in these guidelines include weight loss (excluding postpartum females and intended weight loss for obese animals), anorexia that is not responsive to treatment, diarrhea that is not responsive to treatment, and major organ failure that is not responsive to treatment. Veterinarians use cageside examination in the overall assessment of animals and to aid in the decision to euthanize.To our knowledge, the current study is the first to assess the behavior of critically ill rhesus macaques that controls for the cause of clinical presentation and to use observer presence or absence as an independent variable. To obtain information that may assist in refining clinical endpoints, we compared the behavior of critically ill rhesus macaques while an observer was absent, present, and recently present (labeled as preobservation, observation, and postobservation, respectively, in this text).We hypothesized that in comparison to in-person observation of critically ill rhesus macaques, the use of videotaping in the absence of direct observation would be more accurate in detecting differences in the behavior between those animals that eventually required euthanasia and those that did not. In addition, we hypothesized that behaviors would be suppressed (‘masked’) during direct observation, accounting for the reduced information available to the direct observer. If our hypothesis is supported, then videotaped behavior may be useful as a prognostic indicator that could be incorporated into development of clinical endpoints.  相似文献   
987.
The degradation of aquatic habitats has increasingly become one of the most important factors influencing the distribution of freshwater species worldwide. We analysed the occurrence of three crayfish species, Astacus astacus, Austropotamobius torrentium and Orconectes limosus, in relation to habitat degradation status (based on Directive 2000/60/ES), stream morphology, geographical characteristics and land cover. In total, we analysed 6,768 sites within the Czech Republic (Central Europe), of which 6,187 sites lacked crayfish; among the remainder, A. astacus was present in 507 sites, O. limosus occurred in 44 sites and A. torrentium was present in only 30 sites. The analysis revealed that A. astacus preferred streams of better water quality that were not surrounded by agricultural land or settlements. This species also preferentially occurred in smaller streams with stony bottom substrata that were located at higher altitudes. Austropotamobius torrentium occurrence was associated with the natural character of the water body and the presence of protected areas at higher altitudes. Conversely, the non-native crayfish species O. limosus was typically recorded at lower altitudes in downstream reaches surrounded by agricultural land and with deteriorated water quality. The degree of environmental (human) pressure besides differences in habitat characteristics at sites with ICS and NICS may be of general importance for conservation strategies aimed at central European native crayfish species, primarily because the habitat-driven co-occurrence pattern (and its possible changes in the future) may strongly influence interspecific relationships, such as direct competition and the spread of infectious diseases between crayfish species.  相似文献   
988.
Division of labour is central to the ecological success of eusocial insects, yet the evolutionary factors driving increases in complexity in division of labour are little known. The size–complexity hypothesis proposes that, as larger colonies evolve, both non-reproductive and reproductive division of labour become more complex as workers and queens act to maximize inclusive fitness. Using a statistically robust phylogenetic comparative analysis of social and environmental traits of species within the ant tribe Attini, we show that colony size is positively related to both non-reproductive (worker size variation) and reproductive (queen–worker dimorphism) division of labour. The results also suggested that colony size acts on non-reproductive and reproductive division of labour in different ways. Environmental factors, including measures of variation in temperature and precipitation, had no significant effects on any division of labour measure or colony size. Overall, these results support the size–complexity hypothesis for the evolution of social complexity and division of labour in eusocial insects. Determining the evolutionary drivers of colony size may help contribute to our understanding of the evolution of social complexity.  相似文献   
989.
Attachment of stem leukemic cells to the bone marrow extracellular matrix increases their resistance to chemotherapy and contributes to the disease persistence. In chronic myelogenous leukemia (CML), the activity of the fusion BCR-ABL kinase affects adhesion signaling. Using real-time monitoring of microimpedance, we studied in detail the kinetics of interaction of human CML cells (JURL-MK1, MOLM-7) and of control BCR-ABL-negative leukemia cells (HEL, JURKAT) with fibronectin-coated surface. The effect of two clinically used kinase inhibitors, imatinib (a relatively specific c-ABL inhibitor) and dasatinib (dual ABL/SRC family kinase inhibitor), on cell binding to fibronectin is described. Both imatinib and low-dose (several nM) dasatinib reinforced CML cell interaction with fibronectin while no significant change was induced in BCR-ABL-negative cells. On the other hand, clinically relevant doses of dasatinib (100 nM) had almost no effect in CML cells. The efficiency of the inhibitors in blocking the activity of BCR-ABL and SRC-family kinases was assessed from the extent of phosphorylation at autophosphorylation sites. In both CML cell lines, SRC kinases were found to be transactivated by BCR-ABL. In the intracellular context, EC50 for BCR-ABL inhibition was in subnanomolar range for dasatinib and in submicromolar one for imatinib. EC50 for direct inhibition of LYN kinase was found to be about 20 nM for dasatinib and more than 10 µM for imatinib. Cells pretreated with 100 nM dasatinib were still able to bind to fibronectin and SRC kinases are thus not necessary for the formation of cell-matrix contacts. However, a minimal activity of SRC kinases might be required to mediate the increase in cell adhesivity induced by BCR-ABL inhibition. Indeed, active (autophosphorylated) LYN was found to localize in cell adhesive structures which were visualized using interference reflection microscopy.  相似文献   
990.
Accumulating evidence suggests that cutaneous human papillomavirus (HPV) infection is associated with non-melanoma skin cancer (NMSC). Little is known about the natural history of cutaneous HPV. A sub-cohort of 209 men with no NMSC history, initially enrolled in the HPV infection in men (HIM) study, were followed for a median of 12.6 months. Epidemiological data were collected through self-administered questionnaires. Cutaneous HPV DNA was measured in normal skin swabs (SS) and eyebrow hairs (EB) for 25 and 16 HPV types in genera β and γ, respectively. Any β HPV infection was more prevalent in SS (67.3%) compared to EB (56.5%, p = 0.04). Incidence in SS was higher than 20 per 1,000 person-months for HPV types 4, 5, 23, 38 and 76. Median duration of persistence of β and γ HPV infection was 8.6 and 6.1 months in EB, respectively, and 11.3 months and 6.3 months, in SS, respectively. Older age (>44 years vs. 18-30 years) was significantly associated with prevalent (SS OR = 3.0, 95% CI = 1.2–7.0) and persistent β HPV infection (EB OR = 6.1, 95% CI = 2.6–14.1). History of blistering sunburn was associated with prevalent (OR = 2.8, 95% CI = 1.3–5.8) and persistent (OR = 2.3, 95% CI = 1.2–4.6) β HPV infection in SS. Cutaneous HPV is highly prevalent in men, with age and blistering sunburn being significant risk factors for cutaneous β HPV infection.  相似文献   
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