全文获取类型
收费全文 | 592篇 |
免费 | 69篇 |
专业分类
661篇 |
出版年
2022年 | 8篇 |
2021年 | 10篇 |
2020年 | 3篇 |
2019年 | 10篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 16篇 |
2015年 | 24篇 |
2014年 | 19篇 |
2013年 | 28篇 |
2012年 | 42篇 |
2011年 | 31篇 |
2010年 | 20篇 |
2009年 | 19篇 |
2008年 | 33篇 |
2007年 | 26篇 |
2006年 | 22篇 |
2005年 | 32篇 |
2004年 | 29篇 |
2003年 | 23篇 |
2002年 | 13篇 |
2001年 | 19篇 |
2000年 | 13篇 |
1999年 | 12篇 |
1998年 | 10篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 13篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 12篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 2篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1970年 | 2篇 |
排序方式: 共有661条查询结果,搜索用时 15 毫秒
121.
Chen Y Epperson S Makhsudova L Ito B Suarez J Dillmann W Villarreal F 《American journal of physiology. Heart and circulatory physiology》2004,287(6):H2478-H2486
Cardiac fibroblasts (CF) express adenosine (ADO) receptors, and pharmacological evidence suggests the possible involvement of the A2 (A2a and A2b) receptor (A2aR and A2bR) subtypes in inhibiting cell functions involved in fibrosis. The main objective of this study was to define the contributions of A2a and/or A2b receptors in modulating ADO-induced decreases in CF functions. For this purpose, CF were either treated pharmacologically or had the A2aR or A2bR levels modified through the use of recombinant adenovirus or siRNA. The assessment of mRNA expression in adult rat CF yielded evidence for A1R, A2bR, A2a), and A3R. Endogenously or exogenously enhanced ADO significantly inhibits CF proliferation, collagen, and protein synthesis. A2R and A2aR agonists, although capable of inhibiting CF protein and collagen synthesis, were unable to define the contributions derived from A2aR or A2bR. Overexpression of A2bR in CF yielded significant decreases in basal levels of collagen and protein synthesis and correlated with increases in cAMP levels. However, at higher doses of ADO receptor agonists, significant increases in protein and collagen synthesis were observed. CF with underexpression of A2bR yielded increases in protein and collagen synthesis. In contrast, A2aR underexpression did not modify ADO-induced decreases in CF protein or collagen synthesis. In conclusion, results derived from the molecular manipulation of receptor levels indicate that A2bR are critically involved in ADO-mediated inhibition of CF functions. 相似文献
122.
123.
Santora VJ Covel JA Hayashi R Hofilena BJ Ibarra JB Pulley MD Weinhouse MI Sengupta D Duffield JJ Semple G Webb RR Sage C Ren A Pereira G Knudsen J Edwards JE Suarez M Frazer J Thomsen W Hauser E Whelan K Grottick AJ 《Bioorganic & medicinal chemistry letters》2008,18(4):1490-1494
A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(3) antagonist. Several members of the new series are highly potent and selective binders of rat and human H(3) receptors and display inverse agonism at the human H(3) receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H(3) receptor in an in-vivo pharmacological model. 相似文献
124.
Boyden ED Campos-Xavier AB Kalamajski S Cameron TL Suarez P Tanackovic G Tanackovich G Andria G Ballhausen D Briggs MD Hartley C Cohn DH Davidson HR Hall C Ikegawa S Jouk PS König R Megarbané A Nishimura G Lachman RS Mortier G Rimoin DL Rogers RC Rossi M Sawada H Scott R Unger S Valadares ER Bateman JF Warman ML Superti-Furga A Bonafé L 《American journal of human genetics》2011,(6):767-772
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated. 相似文献
125.
Alfaro C Perez-Gracia JL Suarez N Rodriguez J Fernandez de Sanmamed M Sangro B Martin-Algarra S Calvo A Redrado M Agliano A Gonzalez A Rodriguez I Bolaños E Hervás-Stubbs S Perez-Calvo J Benito A Peñuelas I Vigil C Richter J Martinez-Forero I Melero I 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(11):6130-6142
Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-γ-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing. 相似文献
126.
Joaquín A. Blaya Sonya S. Shin Martin Yagui Carmen Contreras Peter Cegielski Gloria Yale Carmen Suarez Luis Asencios Jaime Bayona Jihoon Kim Hamish S. F. Fraser 《PloS one》2014,9(4)
Background
Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting).Methods
Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient''s treatment; and for that patient to culture convert.Results
1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62–0.72]) and culture (5 vs. 8 days, 0.68 [0.65–0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047).Conclusions
The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system.Trial Registration
ClinicalTrials.gov NCT01201941相似文献127.
Annexins are candidate oviductal receptors for bovine sperm surface proteins and thus may serve to hold bovine sperm in the oviductal reservoir 总被引:2,自引:0,他引:2
The sperm of eutherian mammals are held in a storage reservoir in the caudal segment of the oviduct by binding to the mucosal epithelium. The reservoir serves to maintain the fertility of sperm during storage and to reduce the incidence of polyspermic fertilization. Bovine sperm bind to the epithelium via seminal vesicle secretory proteins in the bovine seminal plasma protein (BSP) family, namely, PDC109 (BSPA1/A2), BSPA3, and BSP30K, which coat the sperm head. Our objective was to identify the receptors for bull sperm on the oviductal epithelium. Proteins extracted from apical plasma membrane preparations of bovine oviductal epithelium were subjected to affinity purification using purified BSPs bound to corresponding antibodies conjugated to Protein A agarose beads. Oviductal protein bands of approximately 34 and 36 kDa were eluted by EGTA from the beads and identified by tandem mass spectrometry as annexins (ANXAs) 1, 2, 4, and 5. Subsequently, antibodies to each of the ANXAs were found to inhibit sperm binding to explants of oviductal epithelium. Anti-ANXA antibodies labeled the apical surfaces and cilia of the mucosal epithelium in sections of bovine oviduct. Western blots confirmed the presence of ANXAs in apical plasma membranes. Because fucose had been determined to be a critical component of the oviductal receptor, the ANXAs were immunoprecipitated from solubilized apical plasma membranes and were probed with Lotus tetragonolobus lectin to verify the presence of fucose. Thus, these ANXAs are strong candidates for the sperm receptors on bovine oviductal epithelium. 相似文献
128.
Trichoderma theobromicola and T. paucisporum: two new species isolated from cacao in South America 总被引:3,自引:0,他引:3
Gary J. Samuels Carmen Suarez Karina Solis Keith A. Holmes Sarah E. Thomas Adnan Ismaiel Harry C. Evans 《Mycological Research》2006,110(4):381-392
Trichoderma theobromicola and T. paucisporum spp. nov. are described. Trichoderma theobromicola was isolated as an endophyte from the trunk of a healthy cacao tree (Theobroma cacao, Malvaceae) in Amazonian Peru; it sporulates profusely on common mycological media. Trichoderma paucisporum is represented by two cultures that were obtained in Ecuador from cacao pods partially infected with frosty pod rot, Moniliophthora roreri; it sporulates sporadically and most cultures remain sterile on common media and autoclaved rice. It sporulates more reliably on synthetic low-nutrient agar (SNA) but produces few conidia. Trichoderma theobromicola was reintroduced into cacao seedlings through shoot inoculation and was recovered from stems but not from leaves, indicating that it is an endophytic species. Both produced a volatile/diffusable antibiotic that inhibited development of M. roreri in vitro and on-pod trials. Neither species demonstrated significant direct in vitro mycoparasitic activity against M. roreri. 相似文献
129.
130.
Hochachka PW Darveau CA Andrews RD Suarez RK 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2003,134(4):675-691
Expanding upon a preliminary communication (Nature 417 (2002) 166), we here further develop a "multiple-causes model" of allometry, where the exponent b is the sum of the influences of multiple contributors to control. The relative strength of each contributor, with its own characteristic value of b(i), is determined by c(i), the control contribution or control coefficient. A more realistic equation for the scaling of metabolism with body size thus can be written as BMR=MR(0)Sigmac(i)(M/M(0))(bi), where MR(0) is the "characteristic metabolic rate" of an animal with a "characteristic body mass", M(0). With M(0) of 1 unit mass (usually kg), MR(0) takes the place of the value a, found in the standard scaling equation, b(i) is the scaling exponent of the process i, and c(i) is its control contribution to overall flux, or the control coefficient of the process i. One can think of this as an allometric cascade, with the b exponent for overall energy metabolism being determined by the b(i) and c(i) values for key steps in the complex pathways of energy demand and energy supply. Key intrinsic factors (such as neural and endocrine processes) or ecological extrinsic factors are considered to act through this system in affecting allometric scaling of energy turnover. Applying this model to maximum vs. BMR data for the first time explains the differing scaling behaviour of these two biological states in mammals, both in the absence and presence of intrinsic regulators such as thyroid hormones (for BMR) and catecholamines (for maximum metabolic rate). 相似文献