全文获取类型
收费全文 | 2552篇 |
免费 | 230篇 |
出版年
2023年 | 18篇 |
2022年 | 27篇 |
2021年 | 61篇 |
2020年 | 32篇 |
2019年 | 47篇 |
2018年 | 45篇 |
2017年 | 70篇 |
2016年 | 63篇 |
2015年 | 107篇 |
2014年 | 137篇 |
2013年 | 180篇 |
2012年 | 220篇 |
2011年 | 178篇 |
2010年 | 116篇 |
2009年 | 91篇 |
2008年 | 127篇 |
2007年 | 139篇 |
2006年 | 143篇 |
2005年 | 121篇 |
2004年 | 128篇 |
2003年 | 97篇 |
2002年 | 110篇 |
2001年 | 49篇 |
2000年 | 39篇 |
1999年 | 40篇 |
1998年 | 28篇 |
1997年 | 20篇 |
1996年 | 22篇 |
1995年 | 20篇 |
1994年 | 16篇 |
1993年 | 16篇 |
1992年 | 29篇 |
1991年 | 16篇 |
1990年 | 19篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 13篇 |
1986年 | 16篇 |
1985年 | 17篇 |
1984年 | 20篇 |
1983年 | 13篇 |
1982年 | 12篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1975年 | 7篇 |
1973年 | 10篇 |
1972年 | 6篇 |
1971年 | 7篇 |
1969年 | 7篇 |
1968年 | 6篇 |
排序方式: 共有2782条查询结果,搜索用时 15 毫秒
1.
Silvio Antoniak Erica M. Sparkenbaugh Michael Tencati Mauricio Rojas Nigel Mackman Rafal Pawlinski 《PloS one》2013,8(11)
Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. 相似文献
2.
Lyndsey R. Buckner Angela M. Amedee Hannah L. Albritton Pamela A. Kozlowski Nedra Lacour Chris L. McGowin Danny J. Schust Alison J. Quayle 《PloS one》2016,11(1)
Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition. 相似文献
3.
4.
Peter Van Bogaert Lieve Peremans Nadine Diltour Danny Van heusden Tinne Dilles Bart Van Rompaey Donna Sullivan Havens 《PloS one》2016,11(4)
The aim of the study reported in this article was to investigate staff nurses’ perceptions and experiences about structural empowerment and perceptions regarding the extent to which structural empowerment supports safe quality patient care. To address the complex needs of patients, staff nurse involvement in clinical and organizational decision-making processes within interdisciplinary care settings is crucial. A qualitative study was conducted using individual semi-structured interviews of 11 staff nurses assigned to medical or surgical units in a 600-bed university hospital in Belgium. During the study period, the hospital was going through an organizational transformation process to move from a classic hierarchical and departmental organizational structure to one that was flat and interdisciplinary. Staff nurses reported experiencing structural empowerment and they were willing to be involved in decision-making processes primarily about patient care within the context of their practice unit. However, participants were not always fully aware of the challenges and the effect of empowerment on their daily practice, the quality of care and patient safety. Ongoing hospital change initiatives supported staff nurses’ involvement in decision-making processes for certain matters but for some decisions, a classic hierarchical and departmental process still remained. Nurses perceived relatively high work demands and at times viewed empowerment as presenting additional. Staff nurses recognized the opportunities structural empowerment provided within their daily practice. Nurse managers and unit climate were seen as crucial for success while lack of time and perceived work demands were viewed as barriers to empowerment. 相似文献
5.
6.
D. Jorquera C. Navarro V. Rojas G. Turra J. Robeson 《Biocontrol Science and Technology》2015,25(8):970-974
We evaluated the effectiveness of phages on meats and goat cheese contaminated with Salmonella Enteritidis (SE). In meats, reductions of SE were observed during the whole experiment, while in goat cheese a reduction was only observed at day 3. We discuss the relevance of phages as a biocontrol in food. 相似文献
7.
It has been known for some time that bicarbonate reverses the inhibition, by formate under HCO3
--depletion conditions, of electron transport in thylakoid membranes. It has been shown that the major effect is on the electron acceptor side of photosystem II, at the site of plastoquinone reduction. After presenting a historical introduction, and a minireview of the bicarbonate effect, we present a hypothesis on how HCO3
- functions in vivo as (a) a proton donor to the plastoquinone reductase site in the D1-D2 protein; and (b) a ligand to Fe2+ in the QA-Fe-QB complex that keeps the D1-D2 proteins in their proper functional conformation. They key points of the hypothesis are: (1) HCO3
- forms a salt bridge between Fe2+ and the D2 protein. The carboxyl group of HCO3
- is a bidentate ligand to Fe2+, while the hydroxyl group H-bonds to a protein residue. (2) A second HCO3
- is involved in protonating a histidine near the QB site to stabilize the negative charge on QB. HCO3
- provides a rapidly available source of H+ for this purpose. (3) After donation of a H+, CO3
2- is replaced by another HCO3
-. The high pKa of CO3
2- ensures rapid reprotonation from the bulk phase. (4) An intramembrane pool of HCO3
- is in equilibrium with a large number of low affinity sites. This pool is a H+ buffering domain functionally connecting the external bulk phase with the quinones. The low affinity sites buffer the intrathylakoid [HCO3
-] against fluctuations in the intracellular CO2. (5) Low pH and high ionic strength are suggested to disrupt the HCO3
- salt bridge between Fe2+ and D2. The resulting conformational change exposes the intramembrane HCO3
- pool and low affinity sites to the bulk phase.Two contrasting hypotheses for the action of formate are: (a) it functions to remove bicarbonate, and the low electron transport left in such samples is due to the left-over (or endogenous) bicarbonate in the system; or (b) bicarbonate is less of an inhibitor and so appears to relieve the inhibition by formate. Hypothesis (a) implies that HCO3
- is an essential requirement for electron transport through the plastoquinones (bound plastoquinones QA and QB and the plastoquinone pool) of photosystem II. Hypothesis (b) implies that HCO3
- does not play any significant role in vivo. Our conclusion is that hypothesis (a) is correct and HCO3
- is an essential requirement for electron transport on the electron acceptor side of PS II. This is based on several observations: (i) since HCO3
-, not CO2, is the active species involved (Blubaugh and Govindjee 1986), the calculated concentration of this species (220 M at pH 8, pH of the stroma) is much higher than the calculated dissociation constant (Kd) of 35–60 M; thus, the likelihood of bound HCO3
- in ambient air is high; (ii) studies on HCO3
- effect in thylakoid samples with different chlorophyll concentrations suggest that the left-over (or endogenous) electron flow in bicarbonate-depleted chloroplasts is due to left-over (or endogenous) HCO3
- remaining bound to the system (Blubaugh 1987).Abbreviations DCMU
3-(3,4-dichlorophenyl)-1, 1-dimethylurea (common name: diuron)
- PSII
photosystem II
- QA
first plastoquinone electron acceptor of PSII
- QB
second plastoquinone acceptor of PS II 相似文献
8.
The effects of bicarbonate buffer (HCO3-/CO2) on the activity of the two K+ channels proposed by some to control the pancreatic B-cell membrane response to glucose were studied. Single K+-channel records from membrane patches of cultured B-cells dissociated from adult rat islets exposed to a glucose- and bicarbonate-free medium (Na-Hepes in place of bicarbonate) exhibit the activity of both the ATP-sensitive as well as the [Ca2+]i-activated K+ channels. However, in the presence of bicarbonate-buffered Krebs solution, the activity of the ATP-sensitive K+ channel is inhibited leaving the activity of the K+ channel activated by intracellular [Ca2+]i unaffected. In the absence of bicarbonate (Hepes/NaOH in place of bicarbonate), lowering the external pH from 7.4 to 7.0 also has differential effects on the two K+ channels. While the K+ channel sensitive to ATP is inhibited, the K+ channel activated by a rise in [Ca2+]i is not affected. To determine whether the response of the B-cell in culture to bicarbonate is also present when the B-cell is functioning within the islet syncytium, the effects of bicarbonate removal on membrane potential of B-cells from intact mouse islets were compared. These studies showed that glucose-evoked electrical activity is also blocked in bicarbonate-free Krebs solution. Furthermore, in the absence of bicarbonate and presence of glucose (11 mM), electrical activity was recovered by lowering the pHo from 7.4 to 7.0. The ATP-sensitive K+-channel activity is greatly reduced by physiologically buffered solutions in pancreatic B-cells in culture. The most likely explanation for the bicarbonate effects is that they are mediated by cytosolic pH changes. Removal of bicarbonate (keeping the external pH at 7.4 with Hepes/NaOH as buffer) would increase the pHi. Since the activity of the [Ca2+]i-dependent K+ channels is not affected by the removal of the bicarbonate buffer, our patch-clamp data in cultured B-cells indicate an involvement of [Ca2+]i-activated K+ channels in the control of the membrane potential. For the B-cell in the islet, we propose that the burst pattern of electrical activity (Ca2+ entry) is controlled, at least in part, by the [Ca2+]i-activated K+ channel. 相似文献
9.
Mansell A. L.; Rojas J. V.; Sillos E. M.; Stolar C. J.; Collins M. H.; Rozovski S. J. 《Journal of applied physiology》1986,61(3):1098-1103
To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity. 相似文献
10.
K A Kennedy P Wilton M Mellander J Rojas H Sundell 《Journal of developmental physiology》1986,8(6):421-433
Fetal lung liquid secretion depends on active transport of chloride ions. Chloride secretion in the stomach is inhibited by epidermal growth factor (EGF). For this reason, the effect of EGF on lung liquid secretion was measured using the impermeant-tracer technique in chronically-prepared fetal sheep. Infusion of EGF over 4 h resulted in decreased lung liquid secretion (from 4.2 +/- 0.6 to 1.7 +/- 0.8 ml/h, P = 0.02) and significant dose related tachycardia. During the infusion, plasma epinephrine levels increased from 27 +/- 5 to 67 +/- 13 pg/ml (P = 0.05) and norepinephrine levels increased from 257 +/- 31 to 544 +/- 69 pg/ml (P = 0.01). Since it is known that beta-adrenergic agonists inhibit lung liquid secretion, subsequent studies were performed with beta-adrenergic blockade using propranolol. Infusion of EGF and propranolol resulted in a significant decrease in lung liquid secretion (from 8.9 +/- 2.1 to 3.0 +/- 1.1 ml/h, P = 0.03). Infusion of propranolol alone had no demonstrable effect on lung liquid secretion. It is concluded that acute EGF infusion increases heart rate and stimulates catecholamine secretion in fetal sheep. EGF also inhibits lung liquid secretion, an effect which appears to be independent of a possible indirect catecholamine effect. 相似文献