全文获取类型
收费全文 | 324317篇 |
免费 | 37859篇 |
国内免费 | 140篇 |
专业分类
362316篇 |
出版年
2018年 | 2831篇 |
2016年 | 3881篇 |
2015年 | 5338篇 |
2014年 | 6275篇 |
2013年 | 8938篇 |
2012年 | 9987篇 |
2011年 | 10122篇 |
2010年 | 6838篇 |
2009年 | 6132篇 |
2008年 | 8861篇 |
2007年 | 9308篇 |
2006年 | 8697篇 |
2005年 | 8422篇 |
2004年 | 8472篇 |
2003年 | 8182篇 |
2002年 | 8068篇 |
2001年 | 14366篇 |
2000年 | 14359篇 |
1999年 | 11542篇 |
1998年 | 4087篇 |
1997年 | 4181篇 |
1996年 | 3964篇 |
1995年 | 3850篇 |
1994年 | 3839篇 |
1993年 | 3729篇 |
1992年 | 9837篇 |
1991年 | 9419篇 |
1990年 | 9246篇 |
1989年 | 8971篇 |
1988年 | 8367篇 |
1987年 | 8030篇 |
1986年 | 7232篇 |
1985年 | 7347篇 |
1984年 | 6080篇 |
1983年 | 5331篇 |
1982年 | 4208篇 |
1981年 | 3725篇 |
1980年 | 3536篇 |
1979年 | 6119篇 |
1978年 | 4573篇 |
1977年 | 4288篇 |
1976年 | 3986篇 |
1975年 | 4309篇 |
1974年 | 4670篇 |
1973年 | 4740篇 |
1972年 | 4373篇 |
1971年 | 4071篇 |
1970年 | 3441篇 |
1969年 | 3341篇 |
1968年 | 2974篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
111.
A method is described to purify pancreatic carboxypeptidases B (CPB), removing contaminating endoproteinases that interfere with use of CPB for carboxy-terminal analysis or modification of proteins. The separation uses zinc chelate chromatography and is based on the property that CPB has higher affinity for immobilized zinc ions than do serine proteinases such as trypsin and chymotrypsin, which are abundant endoproteolytic activities in pancreas. CPB preparations are loaded onto a column of iminodiacetic acid-Sepharose that has been saturated with ZnCl2. A step gradient with buffers of decreasing pH is used to elute bound proteins. CPB elutes at a lower pH than do the serine proteinases. 相似文献
112.
In experiments with CHO-AT3-2 cell culture, a study was made of the effect of potassium cyanate (KNCO) on the effect of gamma radiation and benzo(a)pyrene (BP) by the following tests: cell viability, induction of cells with micronuclei and fragmented nuclei and mutations by thymidine kinase (TK) and Na+/K+-ATPase loci. Some tests have revealed the increase in the effect of gamma radiation and BP produced by potassium cyanate. It is suggested that the sensitizing effects are related to repair system inhibition and/or changes in the cell chromatin structure produced by KNCO. 相似文献
113.
Accumulation and regulation of elastin in the rat uterus 总被引:2,自引:0,他引:2
L Sharrow D Tinker J M Davidson R B Rucker 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1989,192(2):121-126
The relative levels of elastin-specific mRNA were used as a measure of tropoelastin expression in uteri from pregnant Sprague-Dawley rats. The levels of elastin-specific mRNA were also correlated with values for net tropoelastin production and net deposition of mature, crosslinked elastin. The total content of uterine elastin increased throughout gestation, reaching maximal levels at Day 19 of gestation, which were three times those of nongravid tissue. Following involution, the elastin content decreased rapidly to near baseline values by 5 days postpartum. The content of soluble elastin, estimated using an enzyme-linked immunosorbent assay, paralleled in part the increase in elastin deposition and elastin mRNA levels. Uterine elastin metabolism appears to be unlike that in other elastic tissues, e.g., lung and large blood vessels. In most elastin containing tissues, the protein is synthesized during discrete developmental periods and is not readily degraded. However, uterine elastin is continuously expressed, and appears to be in a continual cycle of degradation and replacement. 相似文献
114.
Effects of dinocap on otolith development: evaluation of mouse and hamster fetuses at term 总被引:1,自引:0,他引:1
The morphology of otoliths in CD-1 mouse and Syrian hamster fetuses exposed to the fungicide dinocap were evaluated at the end of gestation. Pregnant mice were dosed by gavage with 0, 10, 15, 30, or 60 mg/kg/day dinocap in corn oil on days 7-16 of gestation. Pregnant hamsters were dosed by the same route with 0, 50, 100, or 200 mg/kg/day on days 7-14 of gestation. At the end of gestation (day 18 in mice, day 15 in hamsters) dams were killed and all fetuses were removed and fixed overnight in 70% ethanol. Fetal heads were then removed, left in 70% ethanol for at least 3 days, and then dehydrated in a graded ethanol series and cleared with methyl salicylate. Otoliths were examined by darkfield microscopy, and each otolith was scored for morphological completeness on a scale of 0 to 3. Otolith development was complete by day 18 of gestation in control mouse fetuses. Otolith development was complete in many, but not all, of the hamster fetuses by day 15 of gestation. In the mouse, dinocap exposure inhibited fetal otolith formation in a dose-related manner, with a significant effect on total otolith score occurring at 10 mg/kg/day and above. Dinocap affected otolith formation in the hamster only at 100 mg/kg/day (200 mg/kg/day was embryolethal), concomitant with severe maternotoxicity and fetotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
115.
B F Hales 《Teratology》1989,40(1):11-20
Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects of phosphoramide mustard are very similar to those of "activated" cyclophosphamide (4-hydroperoxycyclophosphamide). 相似文献
116.
Phorbol esters are known to alter microfilaments but it is not clear if the changes correspond to modulation of the phosphoinositide turnover/protein kinase C system. The novel technique of laser scanning confocal epifluorescence was used to study fiber orientation in phorbol ester treated cells. We treated endothelial cells with control agents and agents known to stimulate protein kinase C: 4 alpha-phorbol, phorbol 12-myristate 13-acetate (PMA), phorbol dibutyrate (PDB), or lipopolysaccharide. After incubation with the test agents, the endothelial cell microfilaments were stained with rhodamine pholloidin and viewed by conventional epifluorescence and by laser scanning confocal epifluorescence microscopy. The images obtained by the confocal microscopy corresponded to a thin optical section through the cells, 300 nm or more in thickness. The microfilaments extended predominantly in the plane of focus. After exposure of the cells to phorbol esters, the stress fibers became more nearly parallel in arrangement or were shortened, but remained in the plane of focus. The modification of microfilaments in response to phorbol esters was quantitated by a single blind analysis. In order to compare the morphological changes with a biochemical action of the phorbol esters, we measured phosphoinositide turnover. The dose-dependence of morphological changes was compared and contrasted to the dose-dependent effect of phorbol esters on bradykinin-stimulated phosphoinositide turnover. PMA had about the same EC50 (1-5 nM) for both biochemical and morphological processes. PDB was less potent in inducing the disruption of microfilament structure than in inhibiting phosphoinositide turnover. Lipopolysaccharide was ineffective in inducing a morphological change under these conditions. A simple activation of protein kinase C is insufficient to explain the dose-dependent effects of phorbol esters. Thus a morphometric analysis can help distinguish the potency of cytoskeleton modulators. 相似文献
117.
E B Arushanian E N Makushkina 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1989,39(6):1129-1133
In female rats various parameters and rhythmical structure of forced swimming underwent unsignificant fluctuations during estrus cycle. Ovariectomy changed the swimming time course and increased the rhythmical index of depression without other serious disturbances of the behavioural "despair" test. After chronic estradiol these shifts were partially eliminated. It is suggested that considerable disturbances of gonadal function may be cause of desynchronousness which facilitated the development of depression. 相似文献
118.
Accumulation of viruslike particles in a yeast mutant lacking a mitochondrial pore protein. 总被引:9,自引:4,他引:5 下载免费PDF全文
M Dihanich E van Tuinen J D Lambris B Marshallsay 《Molecular and cellular biology》1989,9(3):1100-1108
The lack of mitochondrial porin is not lethal in Saccharomyces cerevisiae, but it impairs some respiratory functions and, therefore, growth on nonfermentable carbon sources such as glycerol. However, after a lag phase porinless mutant cells adapt to growth on glycerol, accumulating large amounts of an 86-kilodalton (kDa) protein (M. Dihanich, K. Suda, and G. Schatz, EMBO J. 6:723-728, 1987) and of a 5-kilobase RNA. Immunogold labeling localized the 86 kDa-protein exclusively to the cytosol fraction, although most of it cosedimented with the microsome fraction in earlier cell fractionations. This discrepancy was resolved when the 86-kDa protein was identified as the major coat protein in viruslike particles (VLPs) which is encoded by a double-stranded RNA (L-A RNA). Elimination of VLPs in the original porinless strain by introduction of the mak10 or the mak3 mutation increased the respiratory defect and prolonged its lag phase on nonfermentable carbon sources. The fact that the simultaneous loss of VLPs and respiratory functions are the introduction of mak10 or mak3 occurred even in some porin-containing wild-type strains suggests that there is a link between VLP and mitochondrial functions. 相似文献
119.
Summary The growth of different species of the genera Lactobacillus, Streptococcus, Pediococcus and Leuconostoc was followed in media in which all available iron and copper was chelated by 2,2-dipyridyl. None of the species tested was inhibited in its growth. Iron and copper complexation, by means of chemical scavengers, could be a useful method to direct non-axenic lactic fermentations. 相似文献
120.
At high osmolarity, Escherichia coli synthesizes trehalose intracellularly, irrespective of the nature of the carbon source. Synthesis proceeds via the transfer of UDP-glucose to glucose 6-phosphate, yielding trehalose 6-phosphate, followed by its dephosphorylation to trehalose (H.M. Giaeyer, B.O. Styrvold, I. Kaasen, and A.R. Str?m, J. Bacteriol. 170:2841-2849, 1988). This reaction was exploited to preparatively synthesize [14C]trehalose from exogenous [14C]glucose by using intact bacteria of a mutant (DF214) that could not metabolize glucose. The total yield of radiochemically pure trehalose from glucose was routinely more than 50%. 相似文献