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51.
The progression of primary tumors to metastases remains a significant roadblock to the treatment of most cancers. Emerging evidence has identified genes that specifically affect metastasis and are potential therapeutic targets for managing tumor progression. However, these genes can have dual tumor promoter and suppressor functions that are contextual in manifestation, and that complicate their development as targeted therapies. CD44 and RHAMM/HMMR are examples of multifunctional proteins that can either promote or suppress metastases, as demonstrated in experimental models. These two proteins can be viewed as microenvironmental sensors and this minireview addresses the known mechanistic underpinnings that may determine their metastasis suppressor versus promoter functions. Leveraging this mechanistic knowledge for CD44, RHAMM, and other multifunctional proteins is predicted to improve the precision of therapeutic targeting to achieve more effective management of metastasis. 相似文献
52.
Michiel van Breugel;Frans Bongers;Natalia Norden;Jorge A. Meave;Lucy Amissah;Wirong Chanthorn;Robin Chazdon;Dylan Craven;Caroline Farrior;Jefferson S. Hall;Bruno Hérault;Catarina Jakovac;Edwin Lebrija-Trejos;Miguel Martínez-Ramos;Rodrigo Muñoz;Lourens Poorter;Nadja Rüger;Masha van der Sande;Daisy H. Dent; 《Biological reviews of the Cambridge Philosophical Society》2024,99(3):928-949
The core principle shared by most theories and models of succession is that, following a major disturbance, plant–environment feedback dynamics drive a directional change in the plant community. The most commonly studied feedback loops are those in which the regrowth of the plant community causes changes to the abiotic (e.g. soil nutrients) or biotic (e.g. dispersers) environment, which differentially affect species availability or performance. This, in turn, leads to shifts in the species composition of the plant community. However, there are many other PE feedback loops that potentially drive succession, each of which can be considered a model of succession. 相似文献
53.
54.
With the development of the ICD‐11, the debate about classifying certain psychoactive substances such as antidepressant medication and caffeine as drugs of dependence is ignited again. We argue that any coherent theory of addiction needs to identify the neurobiological processes elicited by a potentially addictive substance and to clearly define the clinical symptoms associated with these processes, which can then be used to guide diagnosis. Tolerance development and withdrawal symptoms can occur with any pharmacologically active agent, and their presence is not a sufficient criterion for the clinical diagnosis of an addictive disorder. Drug craving, drug seeking, and drug consumption in spite of harmful consequences are further key criteria for the diagnosis of substance dependence. Even though these symptoms have been associated with dopamine release in the ventral striatum, ventral striatal dopamine release alone is not a sufficient criterion of the addictive property of a drug. For example, common reinforcers such as food and sex increase dopamine transmission in the nucleus accumbens, but unlike in addictive substances, their effect is regulated by reward predictability and habituation. We emphasize the importance to integrate neurobiological as well as behavioral and clinical effects of a substance to assess its addictive liability. We provide a number of widely discussed examples and a list of key criteria as a conceptual guideline for addiction research and clinical practice. 相似文献
55.
《Addiction biology》2018,23(1):304-312
White matter impairment is associated with opioid dependence. However, the specific neuropathology related to opioid dependence is still not fully understood. The main aims of this study were to: (1) assess the association between white matter impairment and duration of dependence; (2) examine whether this impairment correlates with treatment outcome measures in opioid‐dependent patients post‐detoxification. Fifty‐eight opioid‐dependent patients participated, 20 females and 38 males, across three groups: less than 10 years use (n = 18), 10–15 years use (n = 26) and 16–25+ years use (n = 14). Diffusion tensor imaging was used to assess white matter impairment; whole brain voxel‐wise analysis of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed by Tract‐Based‐Spatial‐Statistics to pinpoint abnormalities in white matter. The longer the subjects were dependent on opioids, the more widespread and severely the white‐matter integrity was disrupted. A general linear model was used to examine patients who relapsed compared to those who were abstinent at follow‐up. No statistical difference was found between groups (p > 0.05). Partial correlations were performed to investigate the relationship between clinical outcome measures (physical health, psychological well being and quality of life and hope for the future) and white‐matter microstructural differences. Significant correlations were found between AD in the posterior corona radiata (L) and MD in the superior longitudinal fasciculus and a clinical measure for HOPE at 9‐month follow‐up. Nevertheless, it must be noted that the calculation of numerous correlations raises the possibility of a type I error, namely; to incorrectly conclude the occurrence of a significant correlation. The ability to investigate the structure–clinical relationship may improve our understanding of the pathological abnormalities associated with opioid dependence and has promise for use in evaluating future therapeutic outcomes in this population. 相似文献
56.
Frank Kalter 《Ethnic and racial studies》2018,41(3):500-508
This contribution compares some major findings of “Spanish Legacies” to findings from the CILS4EU study that has been conducted in four other European countries. Despite the differences in the immigration history and the composition of the immigrant youth, basic results of psychosocial adaptation are surprisingly similar for England, Germany, the Netherlands, and Sweden. This confirms the mostly optimistic picture of the future of the second generation in Europe as drawn for Spain. In a sense, the similarities suggest that the role of the receiving context might be less important than is expected in overarching theoretical frameworks such as “segmented assimilation”. Some aspects of integration that are not covered in “Spanish Legacies” could raise more doubts on the smoothness of the adaptation processes for some immigrants groups. 相似文献
57.
《Addiction biology》2017,22(1):235-245
Pre‐clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol‐dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non‐treatment‐seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light‐to‐moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post‐alcohol administration. However, stimulation was dose‐dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose‐dependently associated with and preceded craving among non‐dependent HD. 相似文献
58.
《Addiction biology》2017,22(3):692-701
Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol‐dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin‐4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol‐dependent rats. Rats were trained to self‐administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed‐dose alcohol, intra‐ventricular agouti‐related protein (endogenous MC4R antagonist), intra‐ventricular HS014 (synthetic MC4R antagonist) and intra‐nasal HS014 on hyperalgesia during withdrawal in alcohol‐dependent rats, relative to non‐dependent drinkers and alcohol‐naïve controls. Alcohol‐dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra‐ventricular and intra‐nasal MC4R antagonists. These manipulations did not affect thermal nociception in non‐dependent drinkers and alcohol‐naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol‐dependent organism. 相似文献
59.
Many mammals have specialized nose-tips with glabrous and often wet skin, called rhinaria. The function of the rhinarium is unknown in most species. Rhinaria differ not only in shape and skin structure, but also in skin temperature. They are considerably colder in carnivorans than in herbivorous artio- and perissodactyls. Domestic dogs are carnivorans and their noses often feel cold, such that they can be used as an abundant and easily accessible model species. We performed a study on rhinarium temperature in dogs under various ambient temperatures as well as in different behavioral and physiological contexts, breeds, and age groups. The rhinaria of adult, alert, and comfortable dogs are colder than ambient temperature from 30 °C (approximately 5 °C colder) down to a break point at about 15 °C. At an ambient temperature of 0 °C, rhinarium temperature is approximately 8 °C and the decrease in skin surface temperature with decreasing ambient temperature has not yet leveled off. The dog rhinarium warms up under a number of circumstances. In contrast to the continuously warm rhinaria of herbivores, our results suggest strongly that the cold state is the operating state of the dog rhinarium. 相似文献
60.
《Insect Conservation and Diversity》2017,10(6):462-471
- As predator and parasitoid insects depend on multiple resources for adult feeding and reproduction, environmental heterogeneity (EH) is expected to be a key driver of their species diversity. In temperate regions, the benefits of EH are expected to vary across spatial scales and seasons, depending on species life‐history traits and temporal fluctuations in resources.
- We tested the importance of EH at multiple spatial scales on diversity and abundance of predator and parasitoid insects, and whether its effects changed across seasons.
- Insect sampling was carried out in highly fragmented landscapes in a Mediterranean region (Tuscany, Central Italy). We selected 18 semi‐natural patches, embedded in an intensive agricultural matrix. For each patch, EH was measured at three spatial scales (micro, patch, and landscape). Five groups of predator and parasitoid insects were sampled 16 times with pan traps between March and November, 2012.
- EH at the landscape scale positively influenced the diversity of predator and parasitoid insects, while the effects at smaller spatial scales were less evident. The strength and the direction of EH˗diversity relationship changed between groups and across seasons, indicating that the mechanisms by which EH affects predators and parasitoids are various and complex.
- Conservation strategies aimed at maximising the diversity of predators and parasitoids should focus more on increasing EH at the landscape scale than at the local scale.