全文获取类型
收费全文 | 448569篇 |
免费 | 39354篇 |
国内免费 | 953篇 |
出版年
2018年 | 16428篇 |
2017年 | 15344篇 |
2016年 | 12581篇 |
2015年 | 6230篇 |
2014年 | 6826篇 |
2013年 | 9657篇 |
2012年 | 15555篇 |
2011年 | 25773篇 |
2010年 | 21236篇 |
2009年 | 16826篇 |
2008年 | 21205篇 |
2007年 | 23689篇 |
2006年 | 9494篇 |
2005年 | 10366篇 |
2004年 | 10307篇 |
2003年 | 10207篇 |
2002年 | 9862篇 |
2001年 | 14840篇 |
2000年 | 14839篇 |
1999年 | 11789篇 |
1998年 | 4274篇 |
1997年 | 4350篇 |
1996年 | 4132篇 |
1995年 | 3964篇 |
1994年 | 3982篇 |
1993年 | 3884篇 |
1992年 | 10050篇 |
1991年 | 9616篇 |
1990年 | 9422篇 |
1989年 | 9123篇 |
1988年 | 8547篇 |
1987年 | 8191篇 |
1986年 | 7402篇 |
1985年 | 7534篇 |
1984年 | 6290篇 |
1983年 | 5507篇 |
1982年 | 4380篇 |
1981年 | 3890篇 |
1980年 | 3716篇 |
1979年 | 6251篇 |
1978年 | 4722篇 |
1977年 | 4407篇 |
1976年 | 4093篇 |
1975年 | 4428篇 |
1974年 | 4807篇 |
1973年 | 4870篇 |
1972年 | 5085篇 |
1971年 | 4740篇 |
1970年 | 3520篇 |
1969年 | 3425篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
B W Glickman 《Génome》1989,31(2):584-589
The excision repair process controlled by the uvrABC gene in Escherichia coli is the major pathway for the repair of a diverse series of DNA damages. To achieve a better understanding of the mechanics of this repair pathway and its impact upon mutagenesis, we have applied a recently developed technology by which the nature of mutation is determined at the DNA sequence level. A comparison of the classes and distribution of mutation in excision-repair-proficient and excision-repair-deficient strains of E. coli reveals that the absence of excision repair can alter both the nature of the mutations recovered as well as their distribution. This can occur in one of several ways. For example, under some circumstances the action of the UvrABC pathway can lead to interruptions of DNA strand continuity and an enhancement of both frameshift and deletion events. Such an effect is seen following damage by psoralen plus near UV (PUVA) treatment that produces crosslinks in the DNA. In comparison, several other treatments produce similar distributions within the classes of mutations recovered but demonstrate an alteration in site specificity. Such is the case following UV irradiation. In this case, the data indicate that while the premutagenic lesions may be the same, mutation fixation in the presence and absence of excision repair may involve different mechanisms. Similarly, evidence from the repair of damage by ethylating agents indicates that while the nature of the mutations recovered is not altered, the preferred location of these events is altered in the absence of excision repair. These results indicate that local DNA sequence can affect on the efficiency of excision repair.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
992.
Abstract A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae, S. pneumoniae and S. pyogenes A produced by intranasal inoculation. Yeast pre-treatment also increased the efficacy of antibiotic therapy in bacterial infections and of antiviral drugs in viral infections. Yeast treatment of animals stimulated phagocytosis, activated the complement system and induced interferon which are likely to represent the main mechanisms of action whereby pretreatment of mice with live S. cerevisiae cells increases resistance to infection. It is concluded that preventive administration of live Saccharomyces cerevisiae cells should be used for increasing resistance to bacterial infections, in particular of the respiratory tract, or to viral infections, as well as an adjunct to antibiotic and antiviral drug therapy. 相似文献
993.
Manuella Strukelj Suzanne Brais Marc J. Mazerolle David Paré Pierre Drapeau 《Ecosystems》2018,21(1):68-84
Litter decomposition is a major driver of carbon (C) and nitrogen (N) cycles in forest ecosystems and has major implications for C sequestration and nutrient availability. However, empirical information regarding long-term decomposition rates of foliage and wood remains rare. In this study, we assessed long-term C and N dynamics (12–13 years) during decomposition of foliage and wood for three boreal tree species, under a range of harvesting intensities and slash treatments. We used model selection based on the second-order Akaike’s Information Criterion to determine which decomposition model had the most support. The double-exponential model provided a good fit to C mass loss for foliage of trembling aspen, white spruce, and balsam fir, as well as aspen wood. These litters underwent a rapid initial phase of leaching and mineralisation, followed by a slow decomposition. In contrast, for spruce and fir wood, the single-exponential model had the most support. The long-term average decay rate of wood was faster than that of foliage for aspen, but not of conifers. However, we found no evidence that fir and spruce wood decomposed at slower rates than the recalcitrant fraction of their foliage. The critical C:N ratios, at which net N mineralisation began, were higher for wood than for foliage. Long-term decay rates following clear-cutting were either similar or faster than those observed in control stands, depending on litter material, tree species, and slash treatment. The critical C:N ratios were reached later and decreased for all conifer litters following stem-only clear-cutting, indicating increased N retention in harvested sites with high slash loads. Partial harvesting had weak effects on C and N dynamics of decaying litters. A comprehensive understanding of the long-term patterns and controls of C and N dynamics following forest disturbance would improve our ability to forecast the implications of forest harvesting for C sequestration and nutrient availability. 相似文献
994.
The direct effects of the inflammatory mediators, histamine (HI) and serotonin (SE), on the glucose metabolism of Hymenolepis diminuta in vitro were studied by analyzing the excretory products from culture media, containing D-1-13C-glucose and various concentrations of HI and/or SE, by 1H-nuclear magnetic resonance (n.m.r.) spectroscopy. The results revealed that HI markedly accelerated the glycolysis process by increasing the amount of lactate production. The increased glycolytic activity was reflected in a concentration-dependent increase in glucose uptake. Excretion of acetate was also stimulated by HI. A low concentration of SE significantly increased succinate, acetate and lactate excretions, whereas a high concentration had little effect on lactate production and significantly decreased succinate and acetate excretions. A combination of HI and SE treatment at a low concentration had no significant effect, but at a high concentration showed an additive effect, with an increase in lactate production, a decrease in succinate production and an increase in glucose uptake. Thus this work confirms that HI and SE directly influence, albeit differently, energy metabolism of the tapeworm H. diminuta. 相似文献
995.
Adherence to extracellular matrix proteins modulates the functional and secretory activities of mononuclear phagocytes, although the mechanisms regulating these adherence-dependent changes are poorly understood. In this study, the ability of rat inflammatory peritoneal macrophages (PM) to adhere to an endothelial cell-derived extracellular matrix or a denatured collagen/fibronectin-coated surface and perform antibody dependent cell cytotoxicity (ADCC) and secrete reactive oxygen intermediates was compared with PM adherent to tissue culture plastic. Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), two major cyclooxygenase products released by inflammatory macrophages, were also measured by PM adherent to the protein coated surfaces. Rat exudate PM were equally adherent to tissue culture plastic or wells coated with either endothelial cell derived matrix or denatured collagen (gelatin)/fibronectin. PM adherent to a denatured collagen/fibronectin-coated wells demonstrated significantly less cytolytic activity (15 +/- 2% lysis) when compared with either tissue culture plastic adherent PM (43 +/- 7% lysis) or PM adherent to extracellular matrix (59 +/- 11% lysis). PM adherent to extracellular matrix released twofold more TxB2 than plastic adherent PM, while PM adherent to denatured collagen/fibronectin released 40% more PGE2 than cells adherent to tissue culture plastic or 80% more PGE2 than PM adherent to the extracellular matrix. PM adherent to denatured collagen/fibronectin release less superoxide anion (27 +/- .9 nmoles/10(6) PM) than PM adherent to either tissue culture plastic (43 +/- 1 nmoles/10(6) PM) or the extracellular matrix (60 +/- 0.5 nmoles/10(6) PM). Furthermore, incubation of plastic adherent PM with exogenous PGE2 reduced superoxide production in a dose-dependent manner. These results demonstrate that the inhibition of ADCC and secretion of reactive oxygen intermediates by PM adherent to a denatured collagen/fibronectin surface correlated with an increased release of the immunosuppressive prostanoid PGE2. Furthermore, the addition of exogenous PGE2 to plastic adherent PM reproduced the depression in ADCC and superoxide anion production observed by PM adherent to a denatured collagen/fibronectin surface. These studies suggest that the increased production and release of PGE2 by inflammatory macrophages adherent to a denatured collagen surface may act to suppress cytotoxic mechanisms and thereby constitutes part of an autocrine feedback mechanism regulating macrophage function during wound injury. 相似文献
996.
997.
998.
Ultraviolet radiation directly induces pigment production by cultured human melanocytes 总被引:10,自引:0,他引:10
In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms. 相似文献
999.
R Kh Iafaev V V Dudareva T G Ivanova E B Kaganer L V Loseva 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1986,(11):16-20
The short-term prognosis of the epidemic situation requires the establishment of the system of constant surveillance, which takes into account the data on morbidity rates for several years, both total and in various age groups, the data on the morbidity level and its changes, induced by meningococci of the epidemic group, in the IV quarter of the year, the data on the level of carriership among the indicator groups of the population in this period, as well as the data on changes in antibody titers in the sera of donor blood samples taken in summer and in December. 相似文献
1000.
To examine the role of the RAD52 recombinational repair pathway in compensating for DNA replication defects in Saccharomyces cerevisiae, we performed a genetic screen to identify mutants that require Rad52p for viability. We isolated 10 mec1 mutations that display synthetic lethality with rad52. These mutations (designated mec1-srf for synthetic lethality with rad-fifty-two) simultaneously cause two types of phenotypes: defects in the checkpoint function of Mec1p and defects in the essential function of Mec1p. Velocity sedimentation in alkaline sucrose gradients revealed that mec1-srf mutants accumulate small single-stranded DNA synthesis intermediates, suggesting that Mec1p is required for the normal progression of DNA synthesis. sml1 suppressor mutations suppress both the accumulation of DNA synthesis intermediates and the requirement for Rad52p in mec1-srf mutants, but they do not suppress the checkpoint defect in mec1-srf mutants. Thus, it appears to be the DNA replication defects in mec1-srf mutants that cause the requirement for Rad52p. By using hydroxyurea to introduce similar DNA replication defects, we found that single-stranded DNA breaks frequently lead to double-stranded DNA breaks that are not rapidly repaired in rad52 mutants. Taken together, these data suggest that the RAD52 recombinational repair pathway is required to prevent or repair double-stranded DNA breaks caused by defective DNA replication in mec1-srf mutants. 相似文献