全文获取类型
收费全文 | 1252篇 |
免费 | 132篇 |
出版年
2022年 | 26篇 |
2021年 | 38篇 |
2020年 | 11篇 |
2019年 | 23篇 |
2018年 | 20篇 |
2017年 | 25篇 |
2016年 | 28篇 |
2015年 | 51篇 |
2014年 | 55篇 |
2013年 | 81篇 |
2012年 | 85篇 |
2011年 | 69篇 |
2010年 | 49篇 |
2009年 | 35篇 |
2008年 | 49篇 |
2007年 | 49篇 |
2006年 | 53篇 |
2005年 | 34篇 |
2004年 | 39篇 |
2003年 | 47篇 |
2002年 | 40篇 |
2001年 | 30篇 |
2000年 | 38篇 |
1999年 | 31篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1992年 | 15篇 |
1991年 | 18篇 |
1990年 | 27篇 |
1989年 | 21篇 |
1988年 | 12篇 |
1987年 | 15篇 |
1986年 | 11篇 |
1985年 | 18篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 13篇 |
1980年 | 19篇 |
1979年 | 13篇 |
1978年 | 7篇 |
1976年 | 9篇 |
1975年 | 11篇 |
1973年 | 6篇 |
1970年 | 7篇 |
1967年 | 6篇 |
1943年 | 6篇 |
排序方式: 共有1384条查询结果,搜索用时 15 毫秒
51.
Prior to the introduction of white‐nose syndrome (WNS) to North America, temperate bats were thought to remain within hibernacula throughout most of the winter. However, recent research has shown that bats in the southeastern United States emerge regularly from hibernation and are active on the landscape, regardless of their WNS status. The relationship between winter activity and susceptibility to WNS has yet to be explored but warrants attention, as it may enable managers to implement targeted management for WNS‐affected species. We investigated this relationship by implanting 1346 passive integrated transponder (PIT) tags in four species that vary in their susceptibility to WNS. Based on PIT‐tag detections, three species entered hibernation from late October to early November. Bats were active at hibernacula entrances on days when midpoint temperatures ranged from −1.94 to 22.78°C (mean midpoint temperature = 8.70 ± 0.33°C). Eastern small‐footed bats (Myotis leibii), a species with low susceptibility to WNS, were active throughout winter, with a significant decrease in activity in mid‐hibernation (December 16 to February 15). Tricolored bats (Perimyotis subflavus), a species that is highly susceptible to WNS, exhibited an increase in activity beginning in mid‐hibernation and extending through late hibernation (February 16 to March 31). Indiana bats (M. sodalis), a species determined to have a medium–high susceptibility to WNS, remained on the landscape into early hibernation (November 1 to December 15), after which we did not record any again until the latter portion of mid‐hibernation. Finally, gray bats (M. grisescens), another species with low susceptibility to WNS, maintained low but regular levels of activity throughout winter. Given these results, we determined that emergence activity from hibernacula during winter is highly variable among bat species and our data will assist wildlife managers to make informed decisions regarding the timing of implementation of species‐specific conservation actions. 相似文献
52.
Trevor R. Gulbrandsen Scott A. Muffly Alan Shamrock Olivia OReilly Nicolas A. Bedard Jesse E. Otero Timothy S. Brown 《The Iowa orthopaedic journal》2022,42(1):127
BackgroundThe direct anterior approach (DAA) for total hip arthroplasty (THA) has been popularized as a less invasive technique, however outcomes within the first year of practice after fellowship have not been investigated. The primary aim was to determine differences in complications and outcomes between DAA and posterior approach (PA) in the first year of practice. The secondary aim was to determine if there was a learning curve factor in DAA and PA after fellowship training.MethodsTHA cases performed by two surgeons during their first year of practice were reviewed. Overall, 181 THAs (91 DAA, 90 PA) in 168 patients, were performed. Intraoperative differences (blood loss, operative time), hospital stay, complications, reoperations, and revisions were compared.ResultsOverall surgical complications were similar between DAA and PA (11% vs. 9%, p=0.64), but complication profiles were different: dislocation (1% vs. 4%, p=0.17), intraoperative femoral fracture (2% vs. 1%, p=0.32), postoperative periprosthetic fractures (2% vs. 3%, p=0.64). neuropraxia (3% vs. 0%, p=0.08). There was no difference in rate of reoperation (1% vs. 3%, p=0.31). There was a difference in rate of revision at final follow-up (0% vs. 6%, p=0.02). DAA consisted of longer operative time (111 vs. 99 minutes; p<0.001), however was only significant in the first 50 cases (p<0.001), while the subsequent cases were similar (p=0.31). There was no difference in the first 50 cases compared to the subsequent cases for either approach regarding blood loss, complications, reoperations, or revisions.ConclusionDAA and PA for THA performed within the first year of practice exhibit similarly low complication rates, but complication profiles are different. In our series, PA did demonstrate a higher risk of revision at final follow-up. A learning curve is not unique to the DAA. Both DAA and PA THA exhibited a learning curve in the first 50 cases performed at the start of a surgeon’s practice. Level of Evidence: III 相似文献
53.
Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism 总被引:7,自引:0,他引:7
Wang JH Manning BJ Wu QD Blankson S Bouchier-Hayes D Redmond HP 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(2):795-804
Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent. 相似文献
54.
Platelet-derived growth factor and transforming growth factor-beta regulate plasminogen activator inhibitor-1 synthesis in vascular smooth muscle cells 总被引:10,自引:0,他引:10
Bovine vascular smooth muscle cells (SMC) were examined for production of plasminogen activator inhibitor-1 (PAI-1) which may play a key role in regulating the fibrinolytic system. Growth-arrested SMC released active PAI (101 arbitrary units (AU)/10(6) cells/24 h) and a latent form of PAI (880 AU/10(6) cells/24 h) into the conditioned medium (CM). The levels of PAI were significant since 880 AU of PAI could inhibit approximately 1 microgram of tissue plasminogen activator. The extracellular matrix of SMC also contained PAI activity; however, the level was 17-fold less than that observed in the CM. SMC-PAI was a rapid inhibitor of tissue plasminogen activator (kass greater than 10(7) M-1 S-1) and was identified as a 45-kDa protein immunologically related to endothelial cell PAI-1. PAI-1 comprised 20 and 30%, respectively, of the newly synthesized protein detected in the CM and extracellular matrix of SMC. The SMC growth modulators, platelet-derived growth factor and transforming growth factor-beta, induced PAI-1 activity and protein synthesis by 2- and 3-fold, respectively, in a dose- and time-dependent manner. The increases in PAI-1 activity and protein synthesis were ascribed to elevated levels of PAI-1 mRNA as judged by Northern blot analysis of total RNA prepared from control and platelet-derived growth factor- and transforming growth factor-beta-treated cells. Increases in PAI-1 mRNA levels were evident 1 h after growth factor treatment and were maximal after 4 h. PAI-1 mRNA levels were unaffected by cycloheximide treatment. The results indicate that SMC synthesize and release PAI-1 which could regulate the normal fibrinolytic environment of the arterial wall. During atherosclerosis or after vascular injury increases in platelet-derived or locally produced mitogens may stimulate further PAI-1 synthesis and generate a prothrombotic state. 相似文献
55.
B Ioannoni S R Mason P E Reilly D J Winzor 《Archives of biochemistry and biophysics》1986,247(2):372-383
The interaction of cimetidine with liver microsomes has been examined by spectral and equilibrium partition studies. First, difference spectroscopy has been used to evaluate the proportion of cytochrome P-450 in rat liver microsomes that exhibits an affinity for cimetidine in the pharmacologically relevant, low micromolar range of drug concentration. The value of 0.45 so obtained has confirmed that a substantial proportion of rat liver cytochrome P-450 has a high binding affinity for this drug. Second, a study of the binding of cimetidine to human liver microsomes by difference spectroscopy and partition equilibrium has detected a similar interaction, thus providing direct support for the postulate that the clinically observed impairment of oxidative drug metabolism may be due in part to inhibition of cytochrome P-450 monooxygenase by cimetidine. Hepatic microsomes from cimetidine-pretreated rats have been shown to exhibit elevated cytochrome P-450 specific content but a decreased proportion of sites with high affinity for the drug; this finding has been shown not to be the consequence of cimetidine-mediated, time-dependent, irreversible monooxygenase inhibition. Although cimetidine pretreatment caused enhanced specific activity of 7-ethoxyresorufin O-dealkylation, the specific activities for O-dealkylation of 7-ethoxycoumarin and 4-nitroanisole were decreased, as were those for the N-dealkylation of morphine, ethylmorphine, aminopyrine, and dimethylnitrosamine. Since cimetidine pretreatment was shown to cause no change in the Michaelis constants for oxidation of morphine or 7-ethoxyresorufin, it is argued that these results provide strong presumptive evidence for changes in the relative abundance of isoenzymes catalyzing these various oxidations. Thus, a dual role of cimetidine, acting both as inhibitor and inducer of the cytochrome P-450 system, is proposed to account for the impaired oxidative metabolism of some drugs that occurs during coadministration with this H2-receptor antagonist. 相似文献
56.
Hjerpe R Thomas Y Chen J Zemla A Curran S Shpiro N Dick LR Kurz T 《The Biochemical journal》2012,441(3):927-936
Ubiquitin and UBL (ubiquitin-like) modifiers are small proteins that covalently modify other proteins to alter their properties or behaviours. Ubiquitin modification (ubiquitylation) targets many substrates, often leading to their proteasomal degradation. NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is the UBL most closely related to ubiquitin, and its best-studied role is the activation of CRLs (cullin-RING ubiquitin ligases) by its conjugation to a conserved C-terminal lysine residue on cullin proteins. The attachment of UBLs requires three UBL-specific enzymes, termed E1, E2 and E3, which are usually well insulated from parallel UBL pathways. In the present study, we report a new mode of NEDD8 conjugation (NEDDylation) whereby the UBL NEDD8 is linked to proteins by ubiquitin enzymes in vivo. We found that this atypical NEDDylation is independent of classical NEDD8 enzymes, conserved from yeast to mammals, and triggered by an increase in the NEDD8 to ubiquitin ratio. In cells, NEDD8 overexpression leads to this type of NEDDylation by increasing the concentration of NEDD8, whereas proteasome inhibition has the same effect by depleting free ubiquitin. We show that bortezomib, a proteasome inhibitor used in cancer therapy, triggers atypical NEDDylation in tissue culture, which suggests that a similar process may occur in patients receiving this treatment. 相似文献
57.
Anne M. Treasure Siobhan Mackenzie Hall Igor Lesko Derek Moore Malvika Sharan Menno van Zaanen Yo Yehudi Anelda van der Walt 《PLoS computational biology》2022,18(5)
In recent years, a wide variety of mentorship programmes targeting issues that cannot be addressed through traditional teaching and learning methods alone have been developed. Mentoring plays significant roles in the growth and development of both mentors and mentees, and the positive impacts of mentoring have been well documented. Mentorship programmes are therefore increasingly being implemented in a wide variety of fields by organisations, academic institutes, businesses, and governments. While there is a growing body of literature on mentoring and mentorship programmes, gaining a clear overview of the field is often challenging. In this article, we therefore provide a concise summary of recommendations to consider when designing and establishing mentorship programmes. These recommendations are based on the collective knowledge and experiences of 4 different emerging and established mentorship programmes and can be adapted across various mentorship settings or contexts. 相似文献
58.
59.
The purpose of this study was to assess and compare the incidence of delayed menarche and menstrual dysfunction among elite ice hockey players and figure skaters. Forty-three ice hockey players (23.5 ± 4.8 years, 68.2 ± 1.2 kg, 1.68 ± 0.01 m) and 39 figure skaters (17.5 ± 3.4 years, 53.7 ± 5.8 kg, 1.64 ± 0.05 m) completed a self-administered questionnaire on their menstrual status and history, training regimens and lifestyle. Age at menarche did not differ significantly between ice hockey players (13.3 ± 1.3 years) and figure skaters (13.7 ± 1.4 years). Menarche was unrelated to nationality, vigorous training premenarche or age at which the athlete began her sport, but was correlated with the age at menarche of the athletes’ mothers (r = 0.39, p < 0.05). Hormonal contraceptives were used by 35% of ice hockey players and 15% of the figure skaters. Amenorrhea and oligomenorrhea were experienced by 7.1% and 38.7% of postmenarcheal, ice hockey players and figure skaters respectively not using hormonal contraceptives. Menstrual dysfunction was associated with both age and age at menarche in the ice hockey players only. Training factors, and psychological pressure were perceived by the athletes to contribute to menstrual dysfunction. A greater training volume, younger age at commencing sport, lower body mass, greater subjective body image pressure and younger biological and gynaecological age were reported among the figure skaters, and were proposed to explain the higher incidence of menstrual dysfunction among the figure skaters compared with the ice hockey players. Figure skaters appear at increased risk of amenorrhea and oligomenorrhea compared with ice hockey players, which may be linked to training and physical characteristics of the sports. 相似文献
60.