全文获取类型
收费全文 | 597篇 |
免费 | 66篇 |
出版年
2021年 | 13篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 17篇 |
2013年 | 34篇 |
2012年 | 34篇 |
2011年 | 31篇 |
2010年 | 21篇 |
2009年 | 14篇 |
2008年 | 25篇 |
2007年 | 34篇 |
2006年 | 24篇 |
2005年 | 24篇 |
2004年 | 24篇 |
2003年 | 22篇 |
2002年 | 29篇 |
2001年 | 20篇 |
2000年 | 13篇 |
1999年 | 18篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 11篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 8篇 |
1972年 | 7篇 |
1971年 | 4篇 |
1968年 | 4篇 |
1967年 | 5篇 |
1960年 | 3篇 |
排序方式: 共有663条查询结果,搜索用时 93 毫秒
21.
David O. Lambeth Gwen R. Ericson Mark A. Yorek Paul D. Ray 《Biochimica et Biophysica Acta (BBA)/General Subjects》1982,719(3):501-508
The influences of buffers and iron chelators on the rate of autoxidation of Fe2+ were examined in the pH range 6.0–7.4. The catalysis by Fe2+ and Fe3+ of the autoxidation of dithiothreitol was also investigated. In buffers which are non- or poor chelators of iron, 0.25 mM Fe2+, and 0.3 mM dithiothreitol when present with iron, oxidize within minutes at pH 7.4 and 30°C. The stability of each increases as the pH is decreased and more than 90% of each remains after 1 h at pH 6.0. In the presence of buffers or oxy-ligands which preferentially and strongly chelate Fe3+ over Fe2+, Fe2+ autoxidizes rapidly in the pH range 6.0–7.4 while dithiothreitol is protected. Ligands which preferentially bind strongly to Fe2+ stabilize both Fe2+ and dithiothreitol at pH 7.4. Dithiothreitol readily reduces Fe3+ in non-chelating buffers or in the presence of strong chelators of Fe2+, however, the ferrous ions produced are prone to reoxidation at higher pH values. These results show that Fe2+ and dithiothreitol are very susceptible to autoxidation in the neutral pH range, and that the rates are strongly influenced by the presence of chelators of Fe2+ and Fe3+. The rapid autoxidations of these species need to be taken into account when designing and interpreting experiments involving Fe2+ or both dithiothreitol and iron. 相似文献
22.
Sepiapterin synthase, the enzyme system responsible for the synthesis of sepiapterin from dihydroneopterin triphosphate, has been partially purified from extracts of the heads of young adult fruit flies (Drosophila melanogaster). The sepiapterin synthase system consists of two components, termed enzyme A (MW 82,000) and enzyme B (MW 36,000). Some of the properties of the enzyme system are as follows: NADPH and a divalent cation, supplied most effectively as MgCl2, are required for activity; optimal activity occurs at pH 7.4 and 30 C; the K
m
for dihydroneopterin triphosphate is 10 µm; and a number of unconjugated pterins, including biopterin and sepiapterin, are inhibitory. Dihydroneopterin cannot be used as substrate in place of dihydroneopterin triphosphate. Evidence is presented in support of a proposed reaction mechanism for the enzymatic conversion of dihydroneopterin triphosphate to sepiapterin in which enzyme A catalyzes the production of a labile intermediate by nonhydrolytic elimination of the phosphates of dihydroneopterin triphosphate, and enzyme B catalyzes the conversion of this intermediate, in the presence of NADPH, to sepiapterin. An analysis of the activity of sepiapterin synthase during development in Drosophila revealed the presence of a small amount of activity in eggs and young larvae and a much larger amount in late pupae and young adults. Sepiapterin synthase activity during development corresponds with the appearance of sepiapterin in the flies. Of a variety of eye color mutants of Drosophila melanogaster tested for sepiapterin synthase activity, only purple (pr) flies contained activity that was significantly lower than that found in the wild-type flies (22% of the wild-type activity). Further studies indicated that the amount of enzyme A activity is low in purple flies, whereas the amount of enzyme B activity is equal to that present in wild-type flies.This work was supported by research grants from the National Institutes of Health (AM03442) and the National Science Foundation (PCM75-19513 A02). G. G. K. was supported as a predoctoral trainee by National Institutes of Health Training Grant GM00515. 相似文献
23.
The cellular location of proteases in Candida albicans 总被引:1,自引:0,他引:1
Vacuoles prepared from yeast cells of Candida albicans were enriched in proteinase ycaB (EC 3.4.21.48) but not in aminopeptidase or beta-glucosidase. Proteinase ycaB, assayed in situ, increased 1.5-fold during starvation whereas aminopeptidase activity decreased by 25%. Proteinase ycaB increased a further 1.5-fold during germ-tube formation. 相似文献
24.
25.
26.
27.
Wen-Qing Li Nan Hu Zhaoming Wang Kai Yu Hua Su Lemin Wang Chaoyu Wang Stephen J. Chanock Laurie Burdett Ti Ding You-Lin Qiao Jin-Hu Fan Yuan Wang Yi Xu Carol Giffen Xiaoqin Xiong Gwen Murphy Margaret A. Tucker Sanford M. Dawsey Neal D. Freedman Christian C. Abnet Alisa M. Goldstein Philip R. Taylor 《PloS one》2013,8(7)
The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10−3). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. 相似文献
28.
Yongqi Deng Zhiwei Yang Gerald W. Shipps Sie-Mun Lo Robert West Joyce Hwa Shuqin Zheng Constance Farley Jean Lachowicz Margaret van Heek Alan S. Bass Dinesh P. Sinha Craig R. Mahon Mark E. Cartwright 《Bioorganic & medicinal chemistry letters》2013,23(3):791-796
Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles. Responding to concerns about target localization and potential mechanism-based side effects, an initial effort was also made to improve liver concentration in an available rat PK model. An advanced compound 17m with a 5-carboxy-2-thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies. 相似文献
29.
30.