全文获取类型
收费全文 | 1501篇 |
免费 | 243篇 |
出版年
2021年 | 19篇 |
2018年 | 22篇 |
2016年 | 19篇 |
2015年 | 37篇 |
2014年 | 31篇 |
2013年 | 54篇 |
2012年 | 58篇 |
2011年 | 65篇 |
2010年 | 53篇 |
2009年 | 44篇 |
2008年 | 64篇 |
2007年 | 56篇 |
2006年 | 44篇 |
2005年 | 55篇 |
2004年 | 56篇 |
2003年 | 58篇 |
2002年 | 47篇 |
2001年 | 46篇 |
2000年 | 57篇 |
1999年 | 34篇 |
1998年 | 17篇 |
1997年 | 18篇 |
1996年 | 23篇 |
1995年 | 24篇 |
1994年 | 19篇 |
1993年 | 21篇 |
1992年 | 32篇 |
1991年 | 59篇 |
1990年 | 38篇 |
1989年 | 29篇 |
1988年 | 30篇 |
1987年 | 31篇 |
1986年 | 25篇 |
1985年 | 19篇 |
1984年 | 22篇 |
1983年 | 21篇 |
1982年 | 17篇 |
1981年 | 20篇 |
1979年 | 25篇 |
1978年 | 20篇 |
1977年 | 17篇 |
1975年 | 17篇 |
1974年 | 16篇 |
1973年 | 15篇 |
1972年 | 18篇 |
1971年 | 16篇 |
1970年 | 20篇 |
1969年 | 15篇 |
1967年 | 20篇 |
1966年 | 16篇 |
排序方式: 共有1744条查询结果,搜索用时 15 毫秒
941.
Daniel P Reay Sheldon I Bastacky Kathryn E Wack Donna B Stolz Paul D Robbins Paula R Clemens 《Molecular medicine (Cambridge, Mass.)》2015,21(1):442-452
In Duchenne muscular dystrophy (DMD) patients and the mdx mouse model of DMD, chronic activation of the classical nuclear factor-κB (NF-κB) pathway contributes to the pathogenesis that causes degeneration of muscle fibers, inflammation and fibrosis. Prior studies demonstrate that inhibition of inhibitor of κB kinase (IKK)-mediated NF-κB activation using l-isomer NF-κB essential modulator (NEMO)-binding domain (NBD) peptide-based approaches reduce muscle pathology in the mdx mouse. For our studies, the NBD peptide is synthesized as a fusion peptide with an eight-lysine (8K) protein transduction domain to facilitate intracellular delivery. We hypothesized that the d-isoform peptide could have a greater effect than the naturally occurring l-isoform peptide due to the longer persistence of the d-isoform peptide in vivo. In this study, we compared systemic treatment with low (1 mg/kg) and high (10 mg/kg) doses of l- and d-isomer 8K-wild-type-NBD peptide in mdx mice. Treatment with both l- or d-isoform 8K-wild-type-NBD peptide resulted in decreased activation of NF-κB and improved histology in skeletal muscle of the mdx mouse. However, we observed kidney toxicity (characterized by proteinuria), increased serum creatinine, activation of NF-κB and pathological changes in kidney cortex that were most severe with treatment with the d-isoform of 8K-wild-type-NBD peptide. The observed toxicity was also seen in normal mice. 相似文献
942.
Amy J. LaCroix Deborah Stabley Rebecca Sahraoui Margaret P. Adam Michele Mehaffey Kelly Kernan Candace T. Myers Carrie Fagerstrom George Anadiotis Yassmine M. Akkari Katherine M. Robbins Karen W. Gripp Wagner A.R. Baratela Michael B. Bober Angela L. Duker Dan Doherty Jennifer C. Dempsey Daniel G. Miller Katia Sol-Church 《American journal of human genetics》2019,104(1):35-44
943.
Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure 总被引:1,自引:0,他引:1
Hambleton M York A Sargent MA Kaiser RA Lorenz JN Robbins J Molkentin JD 《American journal of physiology. Heart and circulatory physiology》2007,293(6):H3768-H3771
Mice null for the gene encoding protein kinase Calpha (Prkca), or mice treated with pharmacologic inhibitors of the PKCalpha/beta/gamma isoforms, show an augmentation in cardiac contractility that appears to be cardioprotective. However, it remains uncertain if PKCalpha itself functions in a myocyte autonomous manner to affect cardioprotection in vivo. Here we generated cardiac myocyte-specific transgenic mice using a tetracycline-inducible system to permit controlled expression of dominant negative PKCalpha in the heart. Consistent with the proposed function of PKCalpha, induction of dominant negative PKCalpha expression in the adult heart enhanced baseline cardiac contractility. This increase in cardiac contractility was associated with a partial protection from long-term decompensation and secondary dilated cardiomyopathy after myocardial infarction injury. Similarly, Prkca null mice were also partially protected from infarction-induced heart failure, although the area of infarction injury was identical to controls. Thus, myocyte autonomous inhibition of PKCalpha protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility. 相似文献
944.
Nishizawa T Shen YT Rossi F Hong C Robbins J Ishikawa Y Sadoshima J Vatner DE Vatner SF 《American journal of physiology. Heart and circulatory physiology》2007,292(2):H971-H975
Both enhanced sympathetic drive and altered autonomic control are involved in the pathogenesis of heart failure. The goal of the present study was to determine the extent to which chronically enhanced sympathetic drive, in the absence of heart failure, alters reflex autonomic control in conscious, transgenic (TG) rabbits with overexpressed cardiac Gsalpha. Nine TG rabbits and seven wild-type (WT) littermates were instrumented with a left ventricular (LV) pressure micromanometer and arterial catheters and studied in the conscious state. Compared with WT rabbits, LV function was enhanced in TG rabbits, as reflected by increased levels of LV dP/dt (5,600 +/- 413 vs. 3,933 +/- 161 mmHg/s). Baseline heart rate was also higher (P < 0.05) in conscious TG (247 +/- 10 beats/min) than in WT (207 +/- 10 beats/min) rabbits and was higher in TG after muscarinic blockade (281 +/- 9 vs. 259 +/- 8 beats/min) or combined beta-adrenergic receptor and muscarinic blockade (251 +/- 6 vs. 225 +/- 9 beats/min). Bradycardia was blunted (P < 0.05), whether induced by intravenous phenylephrine (arterial baroreflex), by cigarette smoke inhalation (nasopharyngeal reflex), or by veratrine administration (Bezold-Jarisch reflex). With veratrine administration, the bradycardia was enhanced in TG for any given decrease in arterial pressure. Thus the chronically enhanced sympathetic drive in TG rabbits with overexpressed cardiac Gsalpha resulted in enhanced LV function and heart rate and impaired reflex autonomic control. The impaired reflex control was generalized, not only affecting the high-pressure arterial baroreflex but also the low-pressure Bezold-Jarisch reflex and the nasopharyngeal reflex. 相似文献
945.
Gilliam-Davis S Payne VS Kasper SO Tommasi EN Robbins ME Diz DI 《American journal of physiology. Heart and circulatory physiology》2007,293(3):H1327-H1333
Fischer-344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (ANG) II type 1 (AT(1)) receptor blocker L-158,809 on plasma and urinary ANG peptide levels, systolic blood pressure (SBP), and indexes of glucose metabolism in 15-mo-old male F344 rats. Young rats at 3 mo of age (n = 8) were compared with two separate groups of older rats: one control group (n = 7) and one group treated with L-158,809 (n = 6) orally (20 mg/l) for 1 yr. SBP was not different between control and treated rats but was higher in young rats. Serum leptin, insulin, and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma ANG I and ANG II were higher in treated than untreated young or older rats, as evidence of effective AT(1) receptor blockade. Urinary ANG II and ANG-(1-7) were higher in controls compared with young animals, and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared with control rats (young: 8 +/- 2 mg/day vs. control: 129 +/- 51 mg/day vs. treated: 9 +/- 3 mg/day, P < 0.05). Long-term AT(1) receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) ANG systems occurs during blockade, and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury, and activation of the intrarenal ANG system during early aging in normotensive animals can be averted by renin-ANG system blockade. 相似文献
946.
Bahassi el M Penner CG Robbins SB Tichy E Feliciano E Yin M Liang L Deng L Tischfield JA Stambrook PJ 《Mutation research》2007,616(1-2):201-209
Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks. 相似文献
947.
Optimizing protein intake as a foraging strategy to maximize mass gain in an omnivore 总被引:2,自引:0,他引:2
Charles T. Robbins Jennifer K. Fortin Karyn D. Rode Sean D. Farley Lisa A. Shipley Laura A. Felicetti 《Oikos》2007,116(10):1675-1682
Energy maximization, time minimization, and linear programming models subject to various constraints have dominated foraging ecology ideas and methods for decades. However, animals must use very complex physiological processes and foraging decisions to ensure fitness that in many cases may not be adequately described by these approaches. An example of this problem occurs when brown bears, Ursus arctos, have access to both abundant salmon and fruit. Salmon are one of the most energy and nutrient dense foods available to bears. Fruits are often high in soluble carbohydrates, low to deficient in many required nutrients, and more difficult to efficiently exploit. Therefore, wild brown bears that fatten primarily on fruits without access to salmon are 50% smaller than salmon-feeding bears. Thus, we predicted based on a linear, energy-maximizing model without dietary interaction effects that wild brown bears with access to both abundant salmon and fruit would feed almost exclusively on salmon. However, wild adult females with or without accompanying offspring foraged three times longer per day on fruit than on salmon. Similarly, the relative dry matter intake of ad libitum apples and salmon by captive, adult brown bears averaged 76±5% fruit and 24±5% salmon. Captive brown bears consuming mixed diets with intermediate dietary protein levels had 60% lower maintenance energy costs, 37% to 139% higher efficiencies of mass gain, and 72% to 520% higher maximum rates of gain than when they consumed either salmon or fruit alone. These relationships were nonlinear functions of dietary protein content in which salmon and fruit provided complementary nutritional resources. Both wild and captive bears attempted to regulate total protein, energy, and carbohydrate intake within a multidimensional intake target that both maximized energy intake and mass gain. 相似文献
948.
Stieber V Robbins M Balamucki C deGuzman A Tatter S Ekstrand K McMullen K Branch C Shaw E Bourland JD Lovato J Munley M Ellis T 《Radiation research》2007,168(2):143-148
Stereotactic radiosurgery (GKRS) using the Leksell Gamma Knife is a treatment option for patients with trigeminal pain. We analyzed a database of 326 GKRS procedures performed over 4.6 years at three discrete dose levels commonly described in the published literature. Logistic regression was used to model the logit of response as a function of treatment time. The resulting coefficient was converted to an estimated probability of response for the shortest and longest treatment times in clinical practice. The two estimated probabilities were then compared to yield the estimated difference in the biologically effective dose (BED) between the two doses, using a modified linear-quadratic model for stereotactic radiosurgery. This difference was used to back-calculate a clinical value for T(1/2), resulting in a range of 1.28-1.77 h for T(1/2). The biological model appeared to accurately predict that, given the doses and treatment times used in general clinical practice, there would be no significant difference in clinical outcome. 相似文献
949.
Hydrobiologia - Beaked whales are cryptic and difficult to study species, often distributed in deep offshore waters and only briefly visible at the surface. A diverse range of cetacean species has... 相似文献
950.
Sofia Gripenberg Yves Basset Owen T. Lewis J. Christopher D. Terry S. Joseph Wright Indira Simn D. Catalina Fernndez Marjorie Cedeo‐Sanchez Marleny Rivera Hctor Barrios John W. Brown Osvaldo Caldern Anthony I. Cognato Jorma Kim Scott E. Miller Geoffrey E. Morse Sara Pinzn‐Navarro Donald L. J. Quicke Robert K. Robbins Juha‐Pekka Salminen Eero Vesterinen 《Ecology letters》2019,22(10):1638-1649
The top‐down and indirect effects of insects on plant communities depend on patterns of host use, which are often poorly documented, particularly in species‐rich tropical forests. At Barro Colorado Island, Panama, we compiled the first food web quantifying trophic interactions between the majority of co‐occurring woody plant species and their internally feeding insect seed predators. Our study is based on more than 200 000 fruits representing 478 plant species, associated with 369 insect species. Insect host‐specificity was remarkably high: only 20% of seed predator species were associated with more than one plant species, while each tree species experienced seed predation from a median of two insect species. Phylogeny, but not plant traits, explained patterns of seed predator attack. These data suggest that seed predators are unlikely to mediate indirect interactions such as apparent competition between plant species, but are consistent with their proposed contribution to maintaining plant diversity via the Janzen–Connell mechanism. 相似文献