全文获取类型
收费全文 | 1623篇 |
免费 | 150篇 |
国内免费 | 48篇 |
专业分类
1821篇 |
出版年
2024年 | 3篇 |
2023年 | 45篇 |
2022年 | 73篇 |
2021年 | 74篇 |
2020年 | 58篇 |
2019年 | 86篇 |
2018年 | 124篇 |
2017年 | 53篇 |
2016年 | 48篇 |
2015年 | 75篇 |
2014年 | 133篇 |
2013年 | 120篇 |
2012年 | 74篇 |
2011年 | 85篇 |
2010年 | 63篇 |
2009年 | 59篇 |
2008年 | 55篇 |
2007年 | 78篇 |
2006年 | 65篇 |
2005年 | 54篇 |
2004年 | 47篇 |
2003年 | 42篇 |
2002年 | 36篇 |
2001年 | 22篇 |
2000年 | 24篇 |
1999年 | 26篇 |
1998年 | 12篇 |
1997年 | 15篇 |
1996年 | 20篇 |
1995年 | 22篇 |
1994年 | 14篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1984年 | 11篇 |
1983年 | 16篇 |
1982年 | 7篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有1821条查询结果,搜索用时 5 毫秒
221.
222.
223.
《Microbes and infection / Institut Pasteur》2014,16(7):571-580
The adipocytes are one of the non-professional phagocytes postulated to be a haven for Mycobacterium tuberculosis during persistence in the human host. The adipocyte – M. tuberculosis interaction data available to date are ex vivo. The present study was primarily aimed to investigate M. tuberculosis infection of adipocytes in course of infection of mouse model. Using primary murine adipocytes, the study first confirmed the infection and immunomodulation of natural adipocytes by M. tuberculosis. The bacilli could be isolated form visceral, subcutaneous, peri renal and mesenteric adipose depots of immunocompetent mice infected with M. tuberculosis intravenously. The bacilli could be isolated from adipocytes and the stromal vascular fraction, even though the numbers were significantly higher in the latter. The bacterial burden in the adipose depots was comparable to those in lungs in the early phase of infection. But with time, the burden in the adipose depots was either decreased or kept under control, despite the increasing burden in the lungs. Infected mice treated with standard anti tubercular drugs, despite effective elimination of bacterial loads in the lungs, continued to harbour M. tuberculosis in adipose depots at loads similar to untreated mice in the late infection phase. 相似文献
224.
Olivia Sveidahl Johansen Tao Ma Jakob Bondo Hansen Lasse Kruse Markussen Renate Schreiber Laia Reverte-Salisa Hua Dong Dan Ploug Christensen Wenfei Sun Thorsten Gnad Iuliia Karavaeva Thomas Svava Nielsen Sander Kooijman Cheryl Cero Oksana Dmytriyeva Yachen Shen Maria Razzoli Shannon L. O’Brien Zachary Gerhart-Hines 《Cell》2021,184(13):3502-3518.e33
225.
Pasarica M Shin AC Yu M Ou Yang HM Rathod M Jen KL MohanKumar S MohanKumar PS Markward N Dhurandhar NV 《Obesity (Silver Spring, Md.)》2006,14(11):1905-1913
Objective: Human adenovirus 36 (Ad‐36) increases adiposity and reduces serum lipids in chicken, mouse, and non‐human primate models, and it is linked to obesity in sero‐epidemiological studies in humans. Involvement of the central nervous system (CNS) or adipose tissue in the mechanism of Ad‐36‐induced adiposity is unknown. The effects of Ad‐36 on adiposity and on the neuroendocrine system were investigated in a rat model. Research Methods and Procedures: Five‐week‐old male Wistar rats were inoculated intraperitoneally with Ad‐36 or medium. Results: Despite similar food intakes, infected rats attained significantly greater body weight and fat pad weight by 30 weeks post‐inoculation. Epididymal‐inguinal, retroperitoneal, and visceral fat pad weights of the infected group were greater by 60%, 46%, and 86%, respectively (p < 0.00001). The fasting serum insulin level and homeostasis model assessment index indicated greater insulin sensitivity in the infected group. Visceral adipose tissue expression of glycerol 3‐phosphate dehydrogenase, peroxisome proliferator‐activated receptor γ, and CCAAT/enhancer‐binding protein α and β was markedly increased in the infected animals compared with controls. Ad‐36 decreased norepinephrine levels significantly in the paraventricular nucleus in infected vs. control rats (mean ± standard error, 8.9 ± 1.1 vs. 12.8 ± 1.2 pg/μg protein; p < 0.05). Ad‐36 markedly decreased serum corticosterone in infected vs. control rats (mean ± standard error, 97 ± 41.0 vs. 221 ± 111 ng/mL; p < 0.005). Discussion: The results suggest that the pro‐adipogenic effect of Ad‐36 may involve peripheral as well as central effects. The male Wistar rat is a good model for the elucidation of metabolic and molecular mechanisms of Ad‐36‐induced adiposity. 相似文献
226.
Nigel J. Fuller Dorothy M. Stirling Stephen Dunnett Gavin P. Reynolds Margaret Ashwell 《Bioscience reports》1987,7(2):121-127
The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake. 相似文献
227.
Summary The mouse adipogenic cell line 1246 which possesses both insulin and insulin-like growth factor I (IGF-I) receptors was used
to investigate the role of IGF-I and insulin on the proliferation of adipocyte precursors and their differentiation into mature
adipocytes. Results indicate that both insulin and IGF-I stimulate the proliferation of the 1246 adipocyte precursors with
IGF-I being slightly more potent than insulin. Dose-response studies indicated that both polypeptides acted at physiological
concentrations corresponding to binding to their own receptors. In contrast, comparison of insulin and IGF-I capacity to stimulate
terminal adipose differentiation indicated that only insulin was active when added at physiological concentrations. IGF-I
could not stimulate adipocyte differentiation except at supraphysiological concentrations (100 ng/ml and above) permitting
its binding to the insulin receptors on 1246 cells. Time course study of expression of early and late markers of adipose differentiation
indicated that the induction of markers such as adipose differentiation-related protein (ADRP), lipoprotein lipase (LPL) and
fatty acid binding protein (FAB) took place even in the absence of insulin. However, the level of early and late differentiation
markers decreased to a level below the one found in undifferentiated cells when cells had been maintained in the absence of
insulin after differentiation had been initiated. These data indicate that although insulin is not necessary for the early
onset of the adipose differentiation program, it is stringently required for the maintenance of the adipocyte phenotype and
cannot be substituted by IGF-I. 相似文献
228.
Mary T. Doan Michael D. Neinast Erika L. Varner Kenneth C. Bedi David Bartee Helen Jiang Sophie Trefely Peining Xu Jay P. Singh Cholsoon Jang J. Eduardo Rame Donita C. Brady Jordan L. Meier Kenneth B. Marguiles Zoltan Arany Nathaniel W. Snyder 《Journal of lipid research》2022,63(6):100224
Anabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of 13C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate. 相似文献
229.
Nina M. Pollak Martina Schweiger Doris Jaeger Dagmar Kolb Manju Kumari Renate Schreiber Stephanie Kolleritsch Philipp Markolin Gernot F. Grabner Christoph Heier Kathrin A. Zierler Thomas Rülicke Robert Zimmermann Achim Lass Rudolf Zechner Guenter Haemmerle 《Journal of lipid research》2013,54(4):1092-1102
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs. 相似文献
230.
Chaldakov GN Beltowsky J Ghenev PI Fiore M Panayotov P Rančič G Aloe L 《Cell biology international》2012,36(3):327-330
Human adipose tissue is partitioned into two large depots (subcutaneous and visceral), and many small depots associated with internal organs, e.g. heart, blood vessels, major lymph nodes, pancreas, prostate gland and ovaries. Since the adipose 'Big Bang' led to the discovery of leptin (Zhang, Proenca, Maffei, Barone, Leopold and Friedman, Nature 1994;372:425-32), adipose tissue has been seen not merely as a lipid store, but as a secretory - endocrine and paracrine - organ, particularly in the pathogenesis of a number of diseases. Accordingly, two major sub-fields of adipobiology have emerged, viz. adipoendocrinology and adipoparacrinology, the latter herein being illustrated by PAAT (periadventitial adipose tissue) in vascular walls. A long-standing paradigm holds that the vascular wall consists of three coats, tunica intima, tunica media and tunica adventitia. It is now imperative that 'to further elucidate vascular function, we should no longer, as hitherto, separate adventitia and PAAT from the vascular wall, but keep them attached and in place, and subject to thorough examination' (Chaldakov, Fiore, Ghenev, Stankulov and Aloe, Int Med J 2000;7:43-9; Chaldakov, Stankulov and Aloe, Atherosclerosis 2001;154:237-8; Chaldakov GN, Stankulov IS, Fiore M, Ghenev PI and Aloe L, Atherosclerosis 2001;159:57-66). From the available data, we propose that it is time to rethink about vascular wall composition, and suggest that the PAAT may be considered the fourth and outermost vascular coat, hence, tunica adiposa (regarding the proximal segment of coronary artery, it is the innermost part of the EAT (epicardial adipose tissue) situated around the coronary adventitia). Its significance in the pathogenesis and therapy of CMDs (cardiometabolic diseases), particularly atherosclerosis and hypertension, requires further basic, translational and clinical studies. 相似文献