全文获取类型
收费全文 | 1380篇 |
免费 | 123篇 |
专业分类
1503篇 |
出版年
2023年 | 9篇 |
2022年 | 24篇 |
2021年 | 32篇 |
2020年 | 27篇 |
2019年 | 29篇 |
2018年 | 33篇 |
2017年 | 32篇 |
2016年 | 31篇 |
2015年 | 72篇 |
2014年 | 74篇 |
2013年 | 95篇 |
2012年 | 121篇 |
2011年 | 97篇 |
2010年 | 51篇 |
2009年 | 47篇 |
2008年 | 60篇 |
2007年 | 73篇 |
2006年 | 71篇 |
2005年 | 55篇 |
2004年 | 54篇 |
2003年 | 43篇 |
2002年 | 41篇 |
2001年 | 10篇 |
2000年 | 27篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 14篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 32篇 |
1991年 | 24篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 18篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 16篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1972年 | 4篇 |
1971年 | 5篇 |
1970年 | 7篇 |
1969年 | 8篇 |
1968年 | 5篇 |
排序方式: 共有1503条查询结果,搜索用时 4 毫秒
91.
Long W Zhang L Longo LD 《American journal of physiology. Regulatory, integrative and comparative physiology》2000,279(3):R860-R873
To test the hypothesis that sarcoplasmic reticulum (SR) Ca(2+) stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca(2+) stores change with development, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal ( approximately 140 days) and nonpregnant adult sheep, we measured NE-induced contraction and intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10(-6) M), the NE-induced responses of tension and [Ca(2+)](i) were 37 +/- 5 and 47 +/- 7%, respectively, of control values (P < 0.01 for each). In the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellular Ca(2+), adult MCA increases in tension and [Ca(2+)](i) were 32 +/- 5 and 13 +/- 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 x 10(-6) to 10(-5) M) resulted in increases in tension and [Ca(2+)](i) in both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca(2+)](i) responses to RYN were essentially eliminated in the presence of zero extracellular Ca(2+). These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca(2+) stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca(2+) flux via plasma membrane L-type Ca(2+) channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca(2+)-activated K(+) channel and/or L-type Ca(2+) channel. 相似文献
92.
Herreros L Rodríguez-Fernandez JL Brown MC Alonso-Lebrero JL Cabañas C Sánchez-Madrid F Longo N Turner CE Sánchez-Mateos P 《The Journal of biological chemistry》2000,275(34):26436-26440
Paxillin is a focal adhesion-associated protein that functions as a multi-domain adapter protein, binding several structural and signaling molecules. alpha-Tubulin was identified as an interacting protein in a two-hybrid screen using the paxillin C-terminal LIM domain as a bait. In vitro binding assays with glutathione S-transferase-paxillin demonstrated an interaction of alpha-tubulin with the C terminus of paxillin. Another member of the tubulin family, gamma-tubulin, bound to both the N and the C terminus of paxillin. The interaction between paxillin and both alpha- and gamma-tubulin in vivo was confirmed by co-immunoprecipitation from human T lymphoblasts. Immunofluorescence studies revealed that, in adherent T cells, paxillin localized to sites of cell-matrix interaction as well as to a large perinuclear region. Confocal microscopy revealed that this region corresponds to the lymphocyte microtubule organizing center, where paxillin colocalizes with alpha- and gamma-tubulin. The localization of paxillin to this area was observed in cells in suspension as well as during adhesion to integrin ligands. These data constitute the first characterization of the interaction of paxillin with the microtubule cytoskeleton, and suggest that paxillin, in addition to its well established role at focal adhesions, could also be associated with the lymphocyte microtubule network. 相似文献
93.
94.
Cristiani F. Bortolatto Cristiano R. Jesse Ethel A. Wilhelm Cristina W. Nogueira 《Life sciences》2010,86(9-10):372-376
AimsStudies have shown that the acute administration of venlafaxine elicits an antidepressant-like effect in the mouse forced swim test (FST) by a mechanism dependent on the l-arginine–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway. Because it has been reported that NO activates different types of potassium (K+) channels in the brain, this study investigated the involvement of K+ channels in the antidepressant-like effect of venlafaxine in the mouse FST.Main methodsMale adult Swiss mice were pretreated with different K+ channel inhibitors or openers 15 min before venlafaxine administration. After 30 min, the open-field test (OFT) and FST were carried out.Key findingsIntracerebroventricular (i.c.v.) pretreatment of mice with subeffective doses of tetraethylammonium (TEA, a non-specific inhibitor of K+ channels, 25 pg/site), glibenclamide (an ATP-sensitive K+ channel inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K+ channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K+ channel inhibitor, 10 pg/site) was able to potentiate the action of a subeffective dose of venlafaxine (2 mg/kg, i.p.). Moreover, the reduction in the immobility time elicited by an effective dose of venlafaxine (8 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with the K+ channel openers cromakalim (10 µg/site, i.c.v.) and minoxidil (10 µg/site, i.c.v.). The drugs used in this study did not produce any change in locomotor activity.SignificanceThe results demonstrate that the neuromodulatory effects of venlafaxine, via the inhibition of K+ channels, are possibly involved in its anti-immobility activity in the mouse FST. 相似文献
95.
Luca Salvatore De Santo Michele Torella Gianpaolo Romano Ciro Maiello Marianna Buonocore Ciro Bancone Alessandro Della Corte Nicola Galdieri Gianantonio Nappi Cristiano Amarelli 《PloS one》2015,10(5)
MethodsData on 362 consecutive recipients (mean age: 47.8±13.7, 20.2% female, 18.2% diabetics, 22.1% with previous cardiac operations, 27.6% hospitalized, 84.9±29.4 ml/min preoperative glomerular filtration rate) were analyzed using multivariable logistic regression modeling. Target outcomes were determinants of troponin release, early graft failure (EGF), acute kidney injury (AKI) and operative death.ResultsMean cTnI release measured 24 hours after transplant was 10.9±11.6 μg/L. Overall hospital mortality was 10.8%, EGF 10.5%, and AKI was 12.2%. cTnI release>10 μg/L proved an independent predictor of EGF (OR 2.2; 95% CI, 1.06–4.6) and AKI (OR 1.031; 95% CI, 1.001-1.064). EGF, in turn, proved a determinant of hospital mortality. Risk factors for cTnI>10 μg/L release were: status 2B (OR 0.35; 95% CI, 0.18-0.69, protective), duration of the ischemic period (OR 1.006; 95% CI, 1.001-1.011), previous cardiac operation (OR 2.9; 95% CI, 1.67-5.0), and left ventricular hypertrophy (OR 3.3; 95% CI, 1.9-5.6).ConclusionsMyocardial enzyme leakage clearly emerged as an epiphenomenon of more complicated clinical course. The complex interplay between surgical procedure features, graft characteristics and recipient end-organ function highlights cTnI release as a risk marker of graft failure and acute kidney injury. The search for optimal myocardial preservation is still an issue. 相似文献
96.
Fernando Henrique Magalh?es Leonardo Abdala Elias Cristiano Rocha da Silva Felipe Fava de Lima Diana Rezende de Toledo André Fabio Kohn 《PloS one》2015,10(11)
Presynaptic inhibition (PSI) has been shown to modulate several neuronal pathways of functional relevance by selectively gating the connections between sensory inputs and spinal motoneurons, thereby regulating the contribution of the stretch reflex circuitry to the ongoing motor activity. In this study, we investigated whether a differential regulation of Ia afferent inflow by PSI may be associated with the performance of two types of plantarflexion sensoriomotor tasks. The subjects (in a seated position) controlled either: 1) the force level exerted by the foot against a rigid restraint (force task, FT); or 2) the angular position of the ankle when sustaining inertial loads (position task, PT) that required the same level of muscle activation observed in FT. Subjects were instructed to maintain their force/position at target levels set at ~10% of maximum isometric voluntary contraction for FT and 90° for PT, while visual feedback of the corresponding force/position signals were provided. Unconditioned H-reflexes (i.e. control reflexes) and H-reflexes conditioned by electrical pulses applied to the common peroneal nerve with conditioning-to-test intervals of 21 ms and 100 ms (corresponding to D1 and D2 inhibitions, respectively) were evoked in a random fashion. A significant main effect for the type of the motor task (FT vs PT) (p = 0.005, η2
p = 0.603) indicated that PTs were undertaken with lower levels of Ia PSI converging onto the soleus motoneuron pool. Additionally, a significant interaction between the type of inhibition (D1 vs D2) and the type of motor task (FT vs PT) (p = 0.038, η2
p = 0.395) indicated that D1 inhibition was associated with a significant reduction in PSI levels from TF to TP (p = 0.001, η2
p = 0.731), whereas no significant difference between the tasks was observed for D2 inhibition (p = 0.078, η2
p = 0.305). These results suggest that D1 and D2 inhibitions of the soleus H-reflex are differentially modulated during the performance of plantarflexion FT and PT. The reduced level of ongoing PSI during PT suggests that, in comparison to FT, there is a larger reliance on inputs from muscle spindles primary afferents when the neuromuscular system is required to maintain position-controlled plantarflexion contractions. 相似文献
97.
Timothy Y. James L. Felipe Toledo Dennis Rödder Domingos da Silva Leite Anat M. Belasen Clarisse M. Betancourt‐Román Thomas S. Jenkinson Claudio Soto‐Azat Carolina Lambertini Ana V. Longo Joice Ruggeri James P. Collins Patricia A. Burrowes Karen R. Lips Kelly R. Zamudio Joyce E. Longcore 《Ecology and evolution》2015,5(18):4079-4097
The amphibian fungal disease chytridiomycosis, which affects species across all continents, recently emerged as one of the greatest threats to biodiversity. Yet, many aspects of the basic biology and epidemiology of the pathogen, Batrachochytrium dendrobatidis (Bd), are still unknown, such as when and from where did Bd emerge and what is its true ecological niche? Here, we review the ecology and evolution of Bd in the Americas and highlight controversies that make this disease so enigmatic. We explore factors associated with variance in severity of epizootics focusing on the disease triangle of host susceptibility, pathogen virulence, and environment. Reevaluating the causes of the panzootic is timely given the wealth of data on Bd prevalence across hosts and communities and the recent discoveries suggesting co‐evolutionary potential of hosts and Bd. We generate a new species distribution model for Bd in the Americas based on over 30,000 records and suggest a novel future research agenda. Instead of focusing on pathogen “hot spots,” we need to identify pathogen “cold spots” so that we can better understand what limits the pathogen''s distribution. Finally, we introduce the concept of “the Ghost of Epizootics Past” to discuss expected patterns in postepizootic host communities. 相似文献
98.
Gustavo Duarte Emiliano N. Calderon Cristiano M. Pereira Laura F. B. Marangoni Henrique F. Santos Raquel S. Peixoto Adalto Bianchini Clovis B. Castro 《Ecology and evolution》2015,5(20):4555-4566
We describe a completely randomizable flow‐through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6× water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open‐source hardware board (Arduino) that was adapted to control heaters and an innovative CO2 injection system. This system reduced seawater pH up to ?0.9 units and increased temperature up to +6°C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40‐day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations. 相似文献
99.
Background
Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death.Aim
LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups.Results
Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation. 相似文献100.
Caterina Longo Simonetta Piana Aimilios Lallas Elvira Moscarella Mara Lombardi Margherita Raucci Giovanni Pellacani Giuseppe Argenziano 《PloS one》2015,10(9)