全文获取类型
收费全文 | 455篇 |
免费 | 60篇 |
专业分类
515篇 |
出版年
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 11篇 |
2016年 | 3篇 |
2015年 | 15篇 |
2014年 | 12篇 |
2013年 | 20篇 |
2012年 | 14篇 |
2011年 | 27篇 |
2010年 | 17篇 |
2009年 | 18篇 |
2008年 | 27篇 |
2007年 | 20篇 |
2006年 | 25篇 |
2005年 | 31篇 |
2004年 | 26篇 |
2003年 | 17篇 |
2002年 | 31篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 11篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 2篇 |
1980年 | 10篇 |
1979年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1965年 | 1篇 |
1961年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有515条查询结果,搜索用时 0 毫秒
1.
2.
Hepatitis B virus (HBV) sequences integrated in the PLC/PRF/5 cell line (Alexander cells), which was derived from a human primary liver carcinoma, were previously extensively studied. Here we describe the analysis of the unoccupied sites of two linearly integrated forms of HBV DNA, AL-14 and AL-26, that were characterized previously. No major cellular DNA rearrangements were seen at the integration sites except for small deletions of host sequences: 2 kilobases of DNA in AL-14 and 17 base pairs (bp) in AL-26. The unoccupied site of AL-26 was found to be missing 182 bp, which previously mapped next to the right end of the integration sites of several independent clones. These were believed to be of cellular origin, but we show here that these 182 bp are in fact from unusual HBV sequences. Surprisingly, a region of this newly detected HBV DNA sequence is more homologous to that of woodchuck HBV DNA. Our analysis shows that the normal counterparts of both AL-14 and AL-26 contain minisatellite-like repetitive sequences. Based on the data presented here and our previous finding of HBV DNA integration at satellite sequences, we propose that genomic simple repetitive sequences are hot spots for HBV DNA integration. 相似文献
3.
Solubilization of Rat Brain Phencyclidine Receptors in an Active Binding Form That Is Sensitive to N-Methyl-d-Aspartate Receptor Ligands 总被引:5,自引:3,他引:2
Phencyclidine (PCP) receptors were successfully solubilized from rat forebrain membranes with 1% sodium cholate. Approximately 58% of the initial protein and 20-30% of the high-affinity PCP binding sites were solubilized. The high affinity toward PCP-like drugs, the stereo-selectivity of the sites, and the sensitivity to N-methyl-D-aspartate (NMDA) receptor ligands were preserved. Binding of the potent PCP receptor ligand N-[3H][1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) to the soluble receptors was saturable (KD = 35 nM), and PCP-like drugs inhibited [3H]TCP binding in a rank order of potency close to that observed for the membrane-bound receptors; the most potent inhibitors were TCP (Ki = 31 nM) and the anticonvulsant MK-801 (Ki = 50 nM). The NMDA receptor antagonist 2-amino-5-phosphonovaleric acid inhibited binding of [3H]TCP to the soluble receptors; glutamate or NMDA diminished this inhibition in a dose-dependent manner. Taken together, the results indicate that the soluble PCP receptor preparation contains the glutamate recognition sites and may represent a single receptor complex for PCP and NMDA, as suggested by electrophysiological data. The successful solubilization of the PCP receptors in an active binding form should now facilitate their purification. 相似文献
4.
Acute Uteroplacental Ischemic Embryo: Lactic Acid Accumulation and Prostaglandin Production in the Fetal Rat Brain 总被引:1,自引:1,他引:0
A new experimental model for studying the effects of acute ischemia on brain development in the near-term fetal rat has been devised. Ischemic conditions are achieved by complete clamping of blood vessels branching from the uterine vasculature into each individual fetus for designated times followed by removal of the clamps to permit reperfusion. Accumulation of lactic acid in the fetal brain depends on the length of the restriction period, reaching a plateau level of 29 mumol/g tissue at about 30 min. It also depends on the reperfusion time. Thus after a period of 15 min of restriction lactate levels show an increase over the next 30-min reperfusion to a value of 25.5 mumol/g followed by a rapid decrease to normal values by 3 h of reperfusion. Restriction of 15 min followed by reperfusion of 45 min causes an elevation of prostaglandin E2 (PGE2) level from 12.4 +/- 0.86 ng/g to 21.1 +/- 0.6 ng/g (p less than 0.001). This elevation in PGE2 level is less apparent after 20 min of restriction. No effects are seen on the level of PGF2 alpha. Both PGE2 and PGF2 alpha accumulate in vitro in a time-dependent manner by brain particulate fraction. In vitro synthesis of both PGE2 and PGF2 alpha is inhibited by indomethacin (100% and 68%, respectively) and AA861 (94% and 76%, respectively). BW755c and nordihydroguaiaretic acid do not affect PGE2 formation but enhance PGF2 alpha production by 112% and 152%, respectively. Particulate fractions from restricted brain produce less PGF2 alpha than control brains (6.38 +/- 1.62 versus 11.43 +/- 2.2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
Increased lysine synthesis in tobacco plants that express high levels of bacterial dihydrodipicolinate synthase in their chloroplasts 总被引:7,自引:2,他引:5
A major nutritional drawback of many crop plants is their low content of several essential amino acids, particularly lysine. The biosynthesis of lysine in plants is regulated by several feedback loops. Dihydrodipicolinate synthase (DHPS) from Escherichia coli, a key enzyme in lysine biosynthesis, which is considerably less sensitive to lysine accumulation than the endogenous plant enzyme has been expressed in chloroplasts of tobacco leaves. Expression of the bacterial enzyme was accompanied by a significant increase in the level of free lysine. No increase in protein-bound lysine was evident. Free lysine accumulation was positively correlated with the level of DHPS activity in various transgenic plants. Compartmentalization of DHPS in the chloroplast was essential for its participation in lysine biosynthesis as no lysine overproduction was obtained in transgenic plants that expressed the bacterial enzyme in the cytoplasm. The elevated level of free lysine in the transgenic plants was sufficient to inhibit, in vivo, a second key enzyme in lysine biosynthesis, namely, aspartate kinase, with no apparent influence on lysine accumulation. The present report not only provides a better understanding of the regulation of lysine biosynthesis in higher plants but also offers a new strategy to improve the production of this essential amino acid. 相似文献
6.
The involvement of transition metal ions in paraquat toxicity was studied in bacterial model system. We show that the addition of micromolar, or lower, concentrations of copper dramatically enhanced the rate of bacterial inactivation. In contrast, the addition of chelating agents totally eliminated the killing of E. coli. No inactivation was observed under anaerobic exposure to paraquat, both in the absence and presence of copper. However, in the presence of copper, the anaerobic addition of hydrogen peroxide resulted in complete restoration of inactivation as under aerobiosis.
Paraquat either produces superoxide ions or directly reduces bound copper ions in a catalytic mode. The reduced cuprous complexes react with hydrogen peroxide to locally form hydroxyl radicals (OH) which are probably responsible for the deleterious effects.
This study indicates the involvement of a site-specific metal-mediated Haber-Weiss mechanism in paraquat toxicity. It is in agreement with earlier observations that copper unusually enhance biological damage induced by either superoxide or ascorbate. 相似文献
Paraquat either produces superoxide ions or directly reduces bound copper ions in a catalytic mode. The reduced cuprous complexes react with hydrogen peroxide to locally form hydroxyl radicals (OH) which are probably responsible for the deleterious effects.
This study indicates the involvement of a site-specific metal-mediated Haber-Weiss mechanism in paraquat toxicity. It is in agreement with earlier observations that copper unusually enhance biological damage induced by either superoxide or ascorbate. 相似文献
7.
8.
Mordechai Schreiber Leon Fogelfeld Miry C. Souroujon Fortune Kohen Sara Fuchs 《Life sciences》1983,33(15):1519-1526
Spiroperidol was covalently conjugated to bovine serum albumin (BSA). Conjugated spiroperidol was almost as efficient as free spiroperidol in its binding capacity to dopamine receptor. Antibodies to spiroperidol were produced in rabbits following repeated immunizations with the conjugate of spiroperidol and BSA. The obtained antibodies have an apparent KD of 0.02 nM for [3H]-spiroperidol. These antibodies bind also to other butyrophenones with IC50 values three to four orders of magnitude higher than the IC50 obtained with unlabeled spiroperidol. Antibodies were purified from anti-spiroperidol sera by affinity chromatography. Anti-idiotypic antibodies were raised in rabbits by immunization with the purified anti-spiroperidol antibodies. Some rabbits produced anti-idiotypic antibodies which bind to rat and calf striatum. 相似文献
9.
10.
Thromboxane and Prostacyclin Levels in Fetal Rabbit Brain and Placenta After Intrauterine Partial Ischemic Episodes 总被引:1,自引:1,他引:0
The appearance of arachidonic acid (AA) oxidation products in fetal rabbit brain and placenta under normal or partial short-term ischemic episodes induced by placental blood vessel restriction was examined. Intracerebral administration of [3H]AA into close-to-term rabbit fetuses gave rise to radioactively labeled prostaglandin (PG) E2, thromboxane B2, and 6-keto-PGF1 alpha metabolites as detected by HPLC analysis. A significant increase of 20-30% of [3H]AA precursor into eicosanoids was detected in brain of fetuses after 2-h restriction. The thromboxane B2 and 6-keto-PGF1 alpha levels were determined by radioimmunoassay technique over a period of 48 h following ischemic episodes. Thromboxane B2 content in affected animals was higher by five- and twofold at 3 h over control fetal brain and placental tissue values, respectively, and remained significantly higher for 24 h. 6-Keto-PGF1 alpha levels reached a peak value that was greater by 2.5- and 1.5-fold at 6 h for the ischemic brain and placental tissue, respectively, compared with control fetuses. PGE2 levels were less affected, attaining a maximum of 1.9- and 1.1-fold in brain and placenta correspondingly. The thromboxane/prostacyclin ratio reached a maximum in the brain after approximately 3 h, while that in the placenta continued to rise even after 20 h. Persisting high levels of thromboxane are indicative of cerebral vasoconstriction and may suggest possible damaging effects. 相似文献