全文获取类型
收费全文 | 529篇 |
免费 | 67篇 |
国内免费 | 1篇 |
出版年
2021年 | 7篇 |
2019年 | 4篇 |
2016年 | 5篇 |
2015年 | 14篇 |
2014年 | 7篇 |
2013年 | 19篇 |
2012年 | 27篇 |
2011年 | 25篇 |
2010年 | 22篇 |
2009年 | 17篇 |
2008年 | 20篇 |
2007年 | 26篇 |
2006年 | 11篇 |
2005年 | 25篇 |
2004年 | 20篇 |
2003年 | 18篇 |
2002年 | 23篇 |
2001年 | 14篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 14篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 20篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1971年 | 5篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1966年 | 4篇 |
1953年 | 4篇 |
排序方式: 共有597条查询结果,搜索用时 15 毫秒
61.
Shelton JR Cutler CE Oliveira M Balzarini J Peterson MA 《Bioorganic & medicinal chemistry》2012,20(2):1008-1019
We have developed efficient methods for the preparation of N(6),5'-bis-ureidoadenosine derivatives and their 5'-carbamoyl-N(6)-ureido congeners. Treatment of 5'-azido-5'-deoxy-N(6)-(N-alkyl or -arylurea)adenosine derivatives (6a-d) with H(2)/Pd-C or Ph(3)P/H(2)O, followed by N-methyl-p-nitrophenylcarbamate gave N(6),5'-bis-ureido products 7a-d in 49-78% yield. Analogous derivatives in the 5'-carbamoyl-N(6)-ureido series were prepared by treatment of 2',3'-bis-O-TBS-adenosine (11) with N-methyl-p-nitrophenylcarbamate followed by acylation with appropriate isocyanates which gave 13a-d in 45-69% yield. A more versatile route for obtaining potentially vast libraries of compounds from both series was achieved by treatment of 5'-N-methylureido- or 5'-N-methylcarbamoyladenosine derivatives with ethylchlorformate to give N(6)-ethoxycarbonyl derivatives (9 and 14) in 55-63% yields, respectively. Simple heating of 9 or 14 in the presence of primary alkyl- or arylamines gave the corresponding N(6),5'-bis-ureido- or 5'-carbamoyl-N(6)-ureidoadenosine derivatives in good yields (33-72% and 39-83%; 10a-e and 15a-e, respectively). Significant antiproliferative activities (IC(50)≈4-10 μg/mL) were observed for a majority of the N(6),5'-bis-ureido derivatives, whereas the 5'-carbamoyl-N(6)-ureido derivatives were generally less active (IC(50) >100 μg/mL). A 2',3'-O-desilylated derivative (5'-amino-5'-deoxy-5'-N-methylureido-N(6)-(N-phenylcarbamoyl)adenosine, 16) was shown to inhibit binding of 16 of 441 protein kinases to immobilized ATP-binding site ligands by 30-40% in a competitive binding assay at 10 μM. Compound 16 was also shown to bind to bone morphogenetic protein receptor 1b (BMPR1b) with a Kd=11.5 ± 0.7 μM. 相似文献
62.
Saskia Schmidt J. Claire Hoving William G. C. Horsnell Helen Mearns Antony J. Cutler Tiroyaone M. Brombacher Frank Brombacher 《PloS one》2012,7(12)
Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (TH2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This TH2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLckcreIL-4Rα−/lox) and IL-4Rα-responsive control mice. Global IL-4Rα−/− mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted TH2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4+ T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα−/− mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility. 相似文献
63.
64.
While long-term fixation and storage of specimens is common and useful for many research projects, it is particularly important for space flight investigations where samples may not be returned to Earth for several months (International Space Station) or years (manned mission to Mars). We examined two critical challenges of space flight experimentation: the effect of long-term fixation on the quality of mouse bone preservation and the preservation of antigens and enzymes for both histochemical and immunohistochemical analyses, and how the animal/sample processing affects the preservation. We show that long-term fixation minimally affects standard histological staining, but that enzyme histochemistry and immunolabeling are greatly compromised. Further, we demonstrate that whole animal preservation is not as suitable as whole leg or stripped leg preservation for long-term fixation and all histological analyses. Overall, we recommend whole leg processing for long-term storage of bone specimens in fixative prior to embedding in plastic for histological examination. 相似文献
65.
Thad E Wilson Robert Carter Michael J Cutler Jian Cui Michael L Smith Craig G Crandall 《Journal of applied physiology》2004,96(2):668-673
The purpose of this study was to identify whether baroreceptor unloading was responsible for less efficient heat loss responses (i.e., skin blood flow and sweat rate) previously reported during inactive compared with active recovery after upright cycle exercise (Carter R III, Wilson TE, Watenpaugh DE, Smith ML, and Crandall CG. J Appl Physiol 93: 1918-1929, 2002). Eight healthy adults performed two 15-min bouts of supine cycle exercise followed by inactive or active (no-load pedaling) supine recovery. Core temperature (T(core)), mean skin temperature (T(sk)), heart rate, mean arterial blood pressure (MAP), thoracic impedance, central venous pressure (n = 4), cutaneous vascular conductance (CVC; laser-Doppler flux/MAP expressed as percentage of maximal vasodilation), and sweat rate were measured throughout exercise and during 5 min of recovery. Exercise bouts were similar in power output, heart rate, T(core), and T(sk). Baroreceptor loading and thermal status were similar during trials because MAP (90 +/- 4, 88 +/- 4 mmHg), thoracic impedance (29 +/- 1, 28 +/- 2 Omega), central venous pressure (5 +/- 1, 4 +/- 1 mmHg), T(core) (37.5 +/- 0.1, 37.5 +/- 0.1 degrees C), and T(sk) (34.1 +/- 0.3, 34.2 +/- 0.2 degrees C) were not significantly different at 3 min of recovery between active and inactive recoveries, respectively; all P > 0.05. At 3 min of recovery, chest CVC was not significantly different between active (25 +/- 6% of maximum) and inactive (28 +/- 6% of maximum; P > 0.05) recovery. In contrast, at this time point, chest sweat rate was higher during active (0.45 +/- 0.16 mg.cm(-2).min(-1)) compared with inactive (0.34 +/- 0.19 mg.cm(-2).min(-1); P < 0.05) recovery. After exercise CVC and sweat rate are differentially controlled, with CVC being primarily influenced by baroreceptor loading status while sweat rate is influenced by other factors. 相似文献
66.
A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism 总被引:7,自引:1,他引:6
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Arking DE Cutler DJ Brune CW Teslovich TM West K Ikeda M Rea A Guy M Lin S Cook EH Chakravarti A 《American journal of human genetics》2008,82(1):160-164
Autism is a childhood neuropsychiatric disorder that, despite exhibiting high heritability, has largely eluded efforts to identify specific genetic variants underlying its etiology. We performed a two-stage genetic study in which genome-wide linkage and family-based association mapping was followed up by association and replication studies in an independent sample. We identified a common polymorphism in contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, that is significantly associated with autism susceptibility. Importantly, the genetic variant displays a parent-of-origin and gender effect recapitulating the inheritance of autism. 相似文献
67.
68.
69.
Conditions for breaking various medically important yeasts using glass beads, 30 ml Corex centrifuge tubes, and a Vortex mixer were determined. From 75–95% ofCandida hyphal cells and all species of yeasts exceptSporothrix schenckii were broken when 10 g of 0.45–0.50 mm glass beads, 50–300 mg of wet cells in 5 ml of buffer, and 90 s of vortexing were employed. Yeasts ofSporothrix schenckii broke more efficiently when 0.25–0.30 mm beads were used. 相似文献
70.
Regional changes in amino acid content in developing rat brain 总被引:7,自引:5,他引:2
Abstract— The content of several amino acids was measured in five discrete regions of the central nervous system of the developing rat, using a [3H]dansylation assay procedure. Both regional differences in amino acid content and regional differences in rate of change of amino acids during maturation were found. Particularly prominent were the maturational changes and high adult contents of glutamic acid in the cerebral cortex, GABA in the hypothalamus, and aspartic acid in the medulla. 相似文献