全文获取类型
收费全文 | 290篇 |
免费 | 13篇 |
专业分类
303篇 |
出版年
2021年 | 5篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 9篇 |
2012年 | 14篇 |
2011年 | 9篇 |
2010年 | 9篇 |
2009年 | 2篇 |
2008年 | 12篇 |
2007年 | 12篇 |
2006年 | 4篇 |
2005年 | 11篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1963年 | 3篇 |
排序方式: 共有303条查询结果,搜索用时 15 毫秒
81.
Crosslinking of the B-cell antigen receptor (BCR) initiates a chain of reactions which culminate in a number of biologic responses, including entry into the cell cycle or cell death. The signals and processes which lead to cell death are slowly being unraveled. Based on the dramatic changes in cell shape which occur during progression of the apoptotic response, activation of cytoskeletal assembly may be critical as this appears to be essential to the mitogenic response. In this study, we demonstrate that crosslinking of the human BCR with anti-IgM antibodies results in the rapid assembly of actin. Our data also suggest that this conversion of G- to F-actin may be a prerequisite for the apoptosis response, as prevention of this conversion by botulinum C2 toxin or cytochalasin D results in rescue of the cells from apoptosis. Prevention of tyrosine kinase activation, disruption of microfilament assembly, and rescue of B lymphocytes from apoptosis imply that tyrosine phosphorylation is needed for both microfilament assembly and apoptosis. In each instance where microfilament assembly is inhibited, anti-IgM-induced activation of the protease CPP32 (caspase) is also inhibited. Taken together, these results suggest that the microfilament system is actively involved in delivering signals for apoptosis. 相似文献
82.
83.
84.
Jo?o?Luiz?S?Moreira Rodrigo?M?Mota Maria?F?Horta Santuza?MR?Teixeira Elisabeth?Neumann Jacques?R?Nicoli álvaro?C?NunesEmail author 《BMC microbiology》2005,5(1):15
Background
The accurate identification of Lactobacillus and other co-isolated bacteria during microbial ecological studies of ecosystems such as the human or animal intestinal tracts and food products is a hard task by phenotypic methods requiring additional tests such as protein and/or lipids profiling. 相似文献85.
Irit Avivi Simona Zisman‐Rozen Shulamit Naor Isabelle Dai David Benhamou Gitit Shahaf Hilla Tabibian‐Keissar Noemie Rosenthal Aviya Rakovsky Ammuri Hanna Arik Shechter Eli Peled Noam Benyamini Ekaterina Dmitrukha Iris Barshack Ramit Mehr Doron Melamed 《Aging cell》2019,18(4)
Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B‐cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B‐cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B‐cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B‐cell compartments. B‐cell depletion in old mice resulted in rejuvenated B‐cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"‐like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B‐cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"‐like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B‐cell compartment in aging, through B‐cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population. 相似文献
86.
Immunological studies of aging. IX. Impaired proliferation of T lymphocytes detected in elderly humans by flow cytometry 总被引:3,自引:0,他引:3
L Staiano-Coico Z Darzynkiewicz M R Melamed M E Weksler 《Journal of immunology (Baltimore, Md. : 1950)》1984,132(4):1788-1792
Lymphocytes from humans over the age of 65 incorporate approximately 50% less tritiated thymidine than do lymphocytes from young donors when cultured with phytohemagglutinin. Because lymphocytes from elderly humans are more sensitive to cell cycle arrest induced by tritiated thymidine, it was impossible to determine to what extent impaired thymidine incorporation reflected a defect in proliferation or the increased sensitivity to the radioactive isotope. Flow cytometry was used to measure the proliferative response of T cells from young and old donors in culture with PHA. It was found that 25 percent fewer lymphocytes from old as compared to young humans enter the G1 or complete the S phase of the cell cycle. However, the rate of progression through the cell cycle by activated cells from young and old humans is comparable. Thus, flow cytometry suggested that the difference in thymidine incorporation by lymphocytes from old and young donors is attributable equally to a proliferative defect and to cell cycle arrest induced by tritiated thymidine. This conclusion was supported by the fact that the relative impairment of thymidine incorporation by lymphocytes from old donors was only one-half as great when a 20-min instead of a 24-hr pulse of tritiated thymidine was used. 相似文献
87.
NM Kouyoumdzian NL Rukavina Mikusic G Cao MR Choi SL Della Penna BE Fernández 《Biotechnic & histochemistry》2016,91(8):510-521
We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue. Water intake, creatinine clearance, diuresis and natriuresis increased in the Na group. Under conditions of sodium overload, tempol increased plasma sodium and protein levels and increased diuresis, natriuresis and sodium excretion. Tempol also decreased water intake without affecting creatinine clearance. AQP1 and eNOS were increased and Ang II decreased in the renal cortex of the Na group, whereas AQP2 was increased in the renal medulla. Nonglycosylated AQP1 and eNOS were increased further in the renal cortex of the Na-T group, whereas AQP2 was decreased in the renal medulla and was localized mainly in the cell membrane. Moreover, p47-phox immunostaining was increased in the hypothalamus of Na group, and this increase was prevented by tempol. Our findings suggest that tempol causes hypernatremia after acute sodium overload by inhibiting the thirst mechanism and facilitating diuresis, despite increasing renal eNOS expression and natriuresis. 相似文献
88.
Navot Galpaz Yosi Burger Tamar Lavee Galil Tzuri Amir Sherman Tal Melamed Ravit Eshed Ayala Meir Vitaly Portnoy Einat Bar Einav Shimoni-Shor Ari Feder Yuval Saar Uzi Saar Fabian Baumkoler Efraim Lewinsohn Arthur A. Schaffer Nurit Katzir Yaakov Tadmor 《Archives of biochemistry and biophysics》2013
In order to broaden the available genetic variation of melon, we developed an ethyl methanesulfonate mutation library in an orange-flesh ‘Charentais’ type melon line that accumulates β-carotene. One mutagenized M2 family segregated for a novel recessive trait, a yellow–orange fruit flesh (‘yofI’). HPLC analysis revealed that ‘yofI’ accumulates pro-lycopene (tetra-cis-lycopene) as its major fruit pigment. The altered carotenoid composition of ‘yofI’ is associated with a significant change of the fruit aroma since cleavage of β-carotene yields different apocarotenoids than the cleavage of pro-lycopene. Normally, pro-lycopene is further isomerized by CRTISO (carotenoid isomerase) to yield all-trans-lycopene, which is further cyclized to β-carotene in melon fruit. Cloning and sequencing of ‘yofI’ CRTISO identified two mRNA sequences which lead to truncated forms of CRTISO. Sequencing of the genomic CRTISO identified an A–T transversion in ‘yofI’ which leads to a premature STOP codon. The early carotenoid pathway genes were up regulated in yofI fruit causing accumulation of other intermediates such as phytoene and ζ-carotene. Total carotenoid levels are only slightly increased in the mutant. Mutants accumulating pro-lycopene have been reported in both tomato and watermelon fruits, however, this is the first report of a non-lycopene accumulating fruit showing this phenomenon. 相似文献
89.
90.
A Myc P DeAngelis M Kimmel M R Melamed Z Darzynkiewicz 《Experimental cell research》1991,192(1):198-202
The cationic fluorochrome rhodamine 123 (R123) is specifically taken up by mitochondria of live cells where it is retained due to the mitochondrial transmembrane potential. After pulse exposure of human normal quiescent or proliferating lymphocytes, human lymphocytic leukemic MOLT cells, and mice leukemic L1210 cells to 10 micrograms/ml of R123, the dye release was studied using flow cytometry. Two distinct phases of R123 release, each following first-order kinetics, were apparent; the half-time of retention for the rapidly and slowly released fractions of R123 was 0.8-1.1 and 2.8-4.2 h, respectively. Simultaneous supravital cell staining with R123 and Hoechst 33342 made it possible to correlate retention of R123 with cell position in the cell cycle. No significant differences were observed in the rate of R123 release from cells in G1 vs S or vs G2 + M phases of the cycle. The data rule out a possibility that the release of R123 is due to periodic depolarization of the mitochondria in the cell as may be postulated by cell cycle models that assume a transient passage of cells through resting phase following division. The observed similar rates of R123 release regardless of cell type or cell cycle phase suggest that the factors affecting the exchange are similar in normal lymphocytes vs leukemic cells and unrelated to cell proliferation rate or phase of the cell cycle. Two distinct rates of R123 release indicate the presence of two kinds of binding sites differing in affinity to the dye. 相似文献