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101.
M A Skinner V R Racaniello G Dunn J Cooper P D Minor J W Almond 《Journal of molecular biology》1989,207(2):379-392
102.
103.
R K Oldham R O Dillman J R Yannelli N M Barth J R Maleckar A Sferruzza R J Cohen D R Minor L Spitler R Birch 《Molecular biotherapy》1991,3(2):68-73
Metastases from patients with solid tumors were harvested from 196 patients for the purpose of growing tumor-derived activated cells (TDAC). Cells were prepared from autologous tumor cultures by incubation with Interleukin-2 (IL-2) followed by repeated exposure to tumor antigen and/or anti-CD3 monoclonal antibody. Initial growth success was achieved in 66%; 45/56 (80%) of these early cultures were subsequently expanded for in vivo therapy. It took a mean of 69.4 +/- 24.0 days to grow TDAC for treatment. Thirty-eight patients were treated with cyclophosphamide (1 g/m2) on day one followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/day) on days 2-5 and approximately 10(11) TDAC on day 2. Patients subsequently received monthly IL-2 as a 96-hour constant infusion if their cancers were stable or regressing. Median age was 51 yrs; 58% were male. Performance status was 0-1 in 64%, 29% had lung metastases; 34% had liver metastases. The usual IL-2 toxicities were seen. Responses were seen only in 1/38 patients (3%); a partial response in a patient with lymphoma. Forty-two percent were stable 90 days post-treatment, the rest were progressive or inevaluable. We conclude that a treatment plan for IL-2/TDAC is technically difficult, costly, and not practical under these conditions. Clinical results to date are not clearly different than those obtained with other IL-2 regimens. 相似文献
104.
Environmental enhancement of in vitro chondrogenesis. IV. Stimulation of somite chondrogenesis by exogenous chondromucoprotein 总被引:11,自引:0,他引:11
Proteoglycan complex extracted from embryonic cartilage (chondromucoprotein) with 4.0 M guanidinium chloride greatly stimulates in vitro somite chondrogenesis. In the presence of exogenous chondromucoprotein (CMP) which consists predominantly of proteochondroitin sulfate, there is a large increase in the amount of differentiating cartilage which can be detected visually in somite explants. There is a 2–3-fold increase in the amount of sulfated glycosaminoglycans (including chondroitin 4- and 6-sulfate) accumulated by somite explants supplied with exogenous CMP complex. These results are of potential significance, since during the period of interaction between the notochord or spinal cord and somitic mesoderm, the notochord and spinal cord synthesize and secrete proteoglycan. 相似文献
105.
106.
Two new species of oribatid mites of the genus Macrogena (Oribatida, Ceratozetidae) are described from alpine soils of the South Island of New Zealand. Macrogena
brevisensilla
sp. n. and Macrogena
abbreviata
sp. n. differ from all species of this genus by the tridactylous legs and by the comparatively short interlamellar setae, respectively. New generic diagnosis and an identification key to the known species of Macrogena are provided. 相似文献
107.
K(2P)2.1 (TREK-1) is a polymodal two-pore domain leak potassium channel that responds to external pH, GPCR-mediated phosphorylation signals, and temperature through the action of distinct sensors within the channel. How the various intracellular and extracellular sensory elements control channel function remains unresolved. Here, we show that the K(2P)2.1 (TREK-1) intracellular C-terminal tail (Ct), a major sensory element of the channel, perceives metabolic and thermal commands and relays them to the extracellular C-type gate through transmembrane helix M4 and pore helix 1. By decoupling Ct from the pore-forming core, we further demonstrate that Ct is the primary heat-sensing element of the channel, whereas, in contrast, the pore domain lacks robust temperature sensitivity. Together, our findings outline a mechanism for signal transduction within K(2P)2.1 (TREK-1) in which there is a clear crosstalk between the C-type gate and intracellular Ct domain. In addition, our findings support the general notion of the existence of modular temperature-sensing domains in temperature-sensitive ion channels. This marked distinction between gating and sensory elements suggests a general design principle that may underlie the function of a variety of temperature-sensitive channels. 相似文献
108.
Rebecca M. Green Fabienne Gally Jonathon G. Keeney Scott Alper Bifeng Gao Min Han Richard J. Martin Andrew R. Weinberger Stephanie R. Case Maisha N. Minor Hong Wei Chu 《PloS one》2009,4(8)
Background
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and lung cancer. Respiratory bacterial infections have been shown to be involved in the development of COPD along with impaired airway innate immunity.Methodology/Principal Findings
To address the in vivo impact of cigarette smoke (CS) exclusively on host innate defense mechanisms, we took advantage of Caenorhabditis elegans (C. elegans), which has an innate immune system but lacks adaptive immune function. Pseudomonas aeruginosa (PA) clearance from intestines of C. elegans was dampened by CS. Microarray analysis identified 6 candidate genes with a 2-fold or greater reduction after CS exposure, that have a human orthologue, and that may participate in innate immunity. To confirm a role of CS-down-regulated genes in the innate immune response to PA, RNA interference (RNAi) by feeding was carried out in C. elegans to inhibit the gene of interest, followed by PA infection to determine if the gene affected innate immunity. Inhibition of lbp-7, which encodes a lipid binding protein, resulted in increased levels of intestinal PA. Primary human bronchial epithelial cells were shown to express mRNA of human Fatty Acid Binding Protein 5 (FABP-5), the human orthologue of lpb-7. Interestingly, FABP-5 mRNA levels from human smokers with COPD were significantly lower (p = 0.036) than those from smokers without COPD. Furthermore, FABP-5 mRNA levels were up-regulated (7-fold) after bacterial (i.e., Mycoplasma pneumoniae) infection in primary human bronchial epithelial cell culture (air-liquid interface culture).Conclusions
Our results suggest that the C. elegans model offers a novel in vivo approach to specifically study innate immune deficiencies resulting from exposure to cigarette smoke, and that results from the nematode may provide insight into human airway epithelial cell biology and cigarette smoke exposure. 相似文献109.
Robert M. Stroud Senyon Choe James Holton H. Ronald Kaback Witek Kwiatkowski Daniel L. Minor Roland Riek Andrej Sali Henning Stahlberg William Harries 《Journal of structural and functional genomics》2009,10(2):193-208
A synopsis of the 2007 annual progress report for the Center for Structures of Membrane Proteins, a specialized center of
the Protein Structure Initiative. 相似文献
110.