全文获取类型
收费全文 | 956篇 |
免费 | 63篇 |
国内免费 | 1篇 |
专业分类
1020篇 |
出版年
2023年 | 3篇 |
2022年 | 16篇 |
2021年 | 16篇 |
2020年 | 19篇 |
2019年 | 18篇 |
2018年 | 25篇 |
2017年 | 16篇 |
2016年 | 30篇 |
2015年 | 38篇 |
2014年 | 60篇 |
2013年 | 70篇 |
2012年 | 71篇 |
2011年 | 72篇 |
2010年 | 43篇 |
2009年 | 31篇 |
2008年 | 45篇 |
2007年 | 57篇 |
2006年 | 55篇 |
2005年 | 44篇 |
2004年 | 44篇 |
2003年 | 46篇 |
2002年 | 32篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 17篇 |
1998年 | 8篇 |
1997年 | 10篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1969年 | 3篇 |
1967年 | 3篇 |
1961年 | 1篇 |
排序方式: 共有1020条查询结果,搜索用时 0 毫秒
71.
Gianluca Storci Pasquale Sansone Sara Mari Gabriele D'Uva Simona Tavolari Tiziana Guarnieri Mario Taffurelli Claudio Ceccarelli Donatella Santini Pasquale Chieco Kenneth B. Marcu Massimiliano Bonafè 《Journal of cellular physiology》2010,225(3):682-691
Extracellular and intracellular mediators of inflammation, such as tumor necrosis factor alpha (TNFα) and NF‐kappaB (NF‐κB), play major roles in breast cancer pathogenesis, progression and relapse. SLUG, a mediator of the epithelial–mesenchymal transition process, is over‐expressed in CD44+/CD24? tumor initiating breast cancer cells and in basal‐like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell‐like gene expression profile. Cancer stem cells also over‐express members of the pro‐inflammatory NF‐κB network, but their functional relationship with SLUG expression in breast cancer cells remains unclear. Here, we show that TNFα treatment of human breast cancer cells up‐regulates SLUG with a dependency on canonical NF‐κB/HIF1α signaling, which is strongly enhanced by p53 inactivation. Moreover, SLUG up‐regulation engenders breast cancer cells with stem cell‐like properties including enhanced expression of CD44 and Jagged‐1 in conjunction with estrogen receptor alpha down‐regulation, growth as mammospheres, and extracellular matrix invasiveness. Our results reveal a molecular mechanism whereby TNFα, a major pro‐inflammatory cytokine, imparts breast cancer cells with stem cell‐like features, which are connected to increased tumor aggressiveness. J. Cell. Physiol. 225: 682–691, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
72.
The mechanisms by which H. pylori colonizes and persists within the gastric mucosa are poorly understood. The induction and maintenance of gastric inflammation appear to depend on the complex interaction between a number of cytokines and chemokines. The gastric immune response observed "in vivo", during H. pylori infection, is characterized by a polarization of Th1 cell type that seems to be responsible for gastric pathology. The purpose of this study was to test the direct effect of H. pylori (live or gentamicin-killed) on human PBMC in order to evaluate the "in vitro" Th1-Th2 balance by monitoring IL-18, IFNgamma and IL-10 production. This study demonstrates for the first time that "in vitro" pretreatment with gentamicin-killed H. pylori of PBMC, followed by infection with live bacteria, downregulates the production of inflammatory cytokines such as IL-18 and IFNgamma Our results provide a possible strategy to restore the immunological disorders determined by H. pylori infection. 相似文献
73.
Flavia Strani Antonio Profico Giorgio Manzi Diana Pushkina Pasquale Raia Raffaele Sardella Daniel DeMiguel 《Ecology and evolution》2018,8(14):7022-7030
Mastication of dietary items with different mechanical properties leaves distinctive microscopic marks on the surface of tooth enamel. The inspection of such marks (dental microwear analysis) is informative about the dietary habitus in fossil as well as in modern species. Dental microwear analysis relies on the morphology, abundance, direction, and distribution of these microscopic marks. We present a new freely available software implementation, MicroWeaR, that, compared to traditional dental microwear tools, allows more rapid, observer error free, and inexpensive quantification and classification of all the microscopic marks (also including for the first time different subtypes of scars). Classification parameters and graphical rendering of the output are fully settable by the user. MicroWeaR includes functions to (a) sample the marks, (b) classify features into categories as pits or scratches and then into their respective subcategories (large pits, coarse scratches, etc.), (c) generate an output table with summary information, and (d) obtain a visual surface‐map where marks are highlighted. We provide a tutorial to reproduce the steps required to perform microwear analysis and to test tool functionalities. Then, we present two case studies to illustrate how MicroWeaR works. The first regards a Miocene great ape obtained from through environmental scanning electron microscope, and other a Pleistocene cervid acquired by a stereomicroscope. 相似文献
74.
Di Lorenzo G Gangemi S Merendino RA Minciullo PL Cannavò SP Martinelli N Mansueto P Rini GB Corrocher R Pacor ML 《Mediators of inflammation》2003,12(2):123-125
The value of CD30 and the soluble circulating fragment of CD30 (sCD30) for atopic dermatitis (AD) remains unclear. In particular, little is known about the effects of age, duration of disease and Scoring Atopic Dermatitis index (SCORAD) on the levels of serum sCD30 in patients affected by AD. In the present study, we have analysed serum sCD30 levels of adult patients affected by AD. The study's population includes 18 non-smoking outpatients, with a diagnosis of AD. As a control group we studied 18 non-atopic subjects from laboratory staff, matched for sex and age. These subjects had no history of AD, urticaria or seasonal or perennial rhinitis or asthma, and had negative skin prick test to a panel of allergens. The sCD30 serum levels were clearly higher in patients affected by AD (14.2+/-9.0 IU/ml) than in healthy subjects (1.2+/-0.8 IU/ml) (p<0.001). No differences were observed between males and females affected by atopic dermatitis, regarding age, duration of disease and SCORAD. Significant correlations were found between serum levels of sCD30 levels and age (r=-0.55; 95% confidence interval (CI) for r (Fisher's z transformed)=-0.81 to -0.12; p=0.01), duration of the disease (months) (r=-0.64; 95% CI for r (Fisher's z transformed)=-0.85 to -0.24; p=0.004) and SCORAD (r=-0.74; 95% CI for r (Fisher's z transformed)=-0.89 to -0.42; p=0.004). As demonstrated by the close correlation with age, duration of disease and SCORAD, serum levels of sCD30 appear to be an additional marker for the follow-up of AD. 相似文献
75.
Serena Voccola Immacolata Polvere Jessica R. Madera Marina Paolucci Ettore Varricchio Gianluca Telesio Piero Porcaro Pasquale Vito Romania Stilo Tiziana Zotti 《Journal of cellular physiology》2020,235(3):1895-1902
CARD14/CARMA2sh (CARMA2sh) is a scaffold protein whose mutations are associated with the onset of human genetic psoriasis and other inflammatory skin disorders. Here we show that the immunomodulatory adapter protein TRAF family member-associated NF-κB activator (TANK) forms a complex with CARMA2sh and MALT1 in a human keratinocytic cell line. We also show that CARMA2 and TANK are individually required to activate the nuclear factor κB (NF-κB) response following exposure to polyinosinic-polycytidylic (poly [I:C]), an agonist of toll-like receptor 3. Finally, we present data indicating that TANK is essential for activation of the TBK1/IRF3 pathway following poly (I:C) stimulation, whereas CARMA2sh functions as a repressor of it. More important, we report that two CARMA2sh mutants associated with psoriasis bind less efficiently to TANK and are therefore less effective in suppressing the TBK1/IRF3 pathway. Overall, our data indicate that TANK and CARMA2sh regulate TLR3 signaling in human keratinocytes, which could play a role in the pathophysiology of psoriasis. 相似文献
76.
It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness. 相似文献
77.
Andrea Cortegiani Vincenzo Russotto Francesca Montalto Pasquale Iozzo Cesira Palmeri Santi Maurizio Raineri Antonino Giarratano 《PloS one》2015,10(5)
High-fidelity simulation (HFS) is a learning method which has proven effective in medical education for technical and non-technical skills. However, its effectiveness for knowledge acquisition is less validated. We performed a randomized study with the primary aim of investigating whether HFS, in association with frontal lessons, would improve knowledge about advanced life support (ALS), in comparison to frontal lessons only among medical students. The secondary aims were to evaluate the effect of HFS on knowledge acquisition of different sections of ALS and personal knowledge perception. Participants answered a pre-test questionnaire consisting of a subjective (evaluating personal perception of knowledge) and an objective section (measuring level of knowledge) containing 100 questions about algorithms, technical skills, team working/early warning scores/communication strategies according to ALS guidelines. All students participated in 3 frontal lessons before being randomized in group S, undergoing a HFS session, and group C, receiving no further interventions. After 10 days from the end of each intervention, both groups answered a questionnaire (post-test) with the same subjective section but a different objective one. The overall number of correct answers of the post-test was significantly higher in group S (mean 74.1, SD 11.2) than in group C (mean 65.5, SD 14.3), p = 0.0017, 95% C.I. 3.34 – 13.9. A significantly higher number of correct answers was reported in group S than in group C for questions investigating knowledge of algorithms (p = 0.0001; 95% C.I 2.22–5.99) and team working/early warning scores/communication strategies (p = 0.0060; 95% C.I 1.13–6.53). Students in group S showed a significantly higher score in the post-test subjective section (p = 0.0074). A lower proportion of students in group S confirmed their perception of knowledge compared to group C (p = 0.0079). HFS showed a beneficial effect on knowledge of ALS among medical students, especially for notions of algorithms and team working/early warning scores/communication. 相似文献
78.
Angelo Campanozzi Sonia Avallone Antonio Barbato Roberto Iacone Ornella Russo Gianpaolo De Filippo Giuseppina D’Angelo Licia Pensabene Basilio Malamisura Gaetano Cecere Maria Micillo Ruggiero Francavilla Anna Tetro Giuliano Lombardi Lisa Tonelli Giuseppe Castellucci Luigi Ferraro Rita Di Biase Antonella Lezo Silvia Salvatore Silvia Paoletti Alfonso Siani Daniela Galeone Pasquale Strazzullo MINISAL-GIRCSI Program Study Group 《PloS one》2015,10(4)
Background
Hypertension is the leading cause of death in developed countries and reduction of salt intake is recommended as a key preventive measure.Objective
To assess the dietary sodium and potassium intakes in a national sample of Italian children and adolescents and to examine their relationships with BMI and blood pressure (BP) in the framework of the MINISAL survey, a program supported by the Italian Ministry of Health.Population and Methods
The study population included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age: 10.1±2.9) who were consecutively recruited in participating National Health Service centers in 10 Italian regions. Electrolyte intake was estimated from 24 hour urine collections tested for completeness by the concomitant measurement of creatinine content. Anthropometric indices and BP were measured with standardized procedures.Results
The average estimated sodium intake was 129 mmol (7.4 g of salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three percent of the boys and 89% of the girls had a consumption higher than the recommended age-specific standard dietary target. The estimated average daily potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over 96% of the boys and 98% of the girls having a potassium intake lower than the recommended adequate intake. The mean sodium/potassium ratio was similar among boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the desirable level. Sodium intake was directly related to age, body mass and BP in the whole population.Conclusions
The Italian pediatric population is characterized by excessive sodium and deficient potassium intake. These data suggest that future campaigns should focus on children and adolescents as a major target in the framework of a population strategy of cardiovascular prevention. 相似文献79.
The secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic β-cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 10 minutes) and low-frequency oscillations (period approx. 1.5 hours). Furthermore, characteristic insulin secretory response to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation; substantial insulin peaks following minimal glucose administration; progressively strengthened insulin secretion response after repeated administration of the same amount of glucose; insulin and glucose characteristic curves after Intra-Venous administration of glucose boli in healthy and pre-diabetic subjects as well as in Type 2 Diabetes Mellitus. Previous modeling of β-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Starting with the seminal work of Grodsky it was hypothesized that the population of pancreatic β-cells, possibly functionally aggregated in islets of Langerhans, could be viewed as a set of independent, similar, but not identical controllers (firing units) with distributed functional parameters. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters. The model’s success in reproducing a diverse array of experiments implies that, in order to understand the macroscopic behaviour of the endocrine pancreas in regulating glycemia, there is no need to hypothesize intrapancreatic pacemakers, influences between different islets of Langerhans, glycolitic-induced oscillations or β-cell sensitivity to the rate of change of glycemia. 相似文献
80.
Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals
Rajeev Kumar Verma Jan Gralla Pascal Pedro Klinger-Gratz Adrian Schankath Simon Jung Pasquale Mordasini Christoph Zubler Marcel Arnold Monika Buehlmann Matthias F. Lang Marwan El-Koussy Kety Hsieh 《PloS one》2015,10(9)