全文获取类型
收费全文 | 4535篇 |
免费 | 389篇 |
国内免费 | 2篇 |
专业分类
4926篇 |
出版年
2024年 | 6篇 |
2023年 | 47篇 |
2022年 | 99篇 |
2021年 | 166篇 |
2020年 | 92篇 |
2019年 | 137篇 |
2018年 | 152篇 |
2017年 | 98篇 |
2016年 | 205篇 |
2015年 | 309篇 |
2014年 | 342篇 |
2013年 | 336篇 |
2012年 | 441篇 |
2011年 | 456篇 |
2010年 | 238篇 |
2009年 | 206篇 |
2008年 | 281篇 |
2007年 | 289篇 |
2006年 | 215篇 |
2005年 | 192篇 |
2004年 | 147篇 |
2003年 | 128篇 |
2002年 | 120篇 |
2001年 | 23篇 |
2000年 | 20篇 |
1999年 | 23篇 |
1998年 | 18篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1983年 | 4篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 3篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1961年 | 3篇 |
1960年 | 3篇 |
1955年 | 4篇 |
1911年 | 2篇 |
排序方式: 共有4926条查询结果,搜索用时 15 毫秒
11.
Ann E. Aust Michael R. Antczak Veronica M. Maher J. Justin McCormick 《Journal of cellular biochemistry》1981,16(3):269-279
Human cells that appear capable of metabolizing various classes of carcinogens have been identified using one of two methods: metabolism of tritiated benzo(a)pyrene to aqueous-acetone soluble forms or inhibition of cellular DNA synthesis. Each of the assay systems was optimized and the results on 15 human epithelial cell lines were compared. One or more cell lines were found to activate each of four classes of carcinogens examined: polycyclic hydrocarbons, aromatic amines, heterocyclic hydrocarbons, and nitrosamines. Cells that appeared capable of metabolizing polycyclic hydrocarbons or aromatic amines by these methods were also found to produce metabolites which were cytotoxic to cocultivated human xeroderma pigmentosum fibroblasts after a 48-hr exposure to the carcinogen. 相似文献
12.
Veronica M. Maher J. Justin McCormick Phillip L. Grover Peter Sims 《Mutation research》1977,43(1):117-137
The cytotoxicity of the “K-region” epoxides as well as several other reactive metabolites or chemical derivatives of polycyclic hydrocarbons was compared in normally-repairing human diploid skin fibroblasts and in fibroblasts from a classical xeroderma pigmentosum (XP) patient (XP2BE) whose cells have been shown to carry out excision repair of damage induced in DNA by ultraviolet (UV) radiation at a rate approx. 20% that of normal cells. Each compound tested exhibited a 2- to 3-fold greater cytotoxicity in this XP strain than in the normal strain. To determine whether this difference in survival reflected a difference in the capacity of the strains to repair DNA damage caused by such hydrocarbon derivatives, we compared the cytotoxic effect of several “K-region” epoxides in two additional XP strains, each with a different capacity for repair of UV damage. The ration of the slopes of the survival curves for each of the XP strains to that of the normal strain, following exposure to each epoxide, was very similar to that which we had previously determined for their respective UV curves, suggesting that human cells repair damage induced in DNA by exposure to hydrocarbon derivatives with the same system used for UV-induced lesions.To determine whether the deficiency in rate of excision repair in this classical XP strain (XP2BE) causes such cells to be abnormally susceptible to mutations induced by “K-region” epoxides of polycyclic hydrocarbons, we compared them with normal cells for the frequency of induced mutations to 8-azaguanine resistance. The XP cells were two to three times more susceptible to mutations induced by the “K-region” epoxide of benzo(a)pyrene (BP), 7,12-dimethylbenz(a)anthracene (DMBA), and dibenz(a,h)anthracene (DBA). Evidence also was obtained that cells from an XP variant patient are abnormally susceptible to mutations induced by hydrocarbon epoxides and, as is the case following exposure to UV, are abnormally slow in converting low molecular weight DNA, synthesized from a template following exposure to hydrocarbon epoxides, into large-size DNA. 相似文献
13.
In this study we present data on the partial biological and biochemical characterization of guinea pig leukocyte migration inhibition factor (LIF) and migration inhibition factor (MIF). The results indicate that guinea pig LIF and MIF are distinct mediators of cellular immunity, in terms of indicator cells affected and molecular weight. This is in agreement with previous reports showing distinctions between human LIF and MIF. Partial characterization of guinea pig LIF suggested that it is a heat-stable protein of molecular weight 68,000–158,000 and does not contain terminal sialic acid groups. 相似文献
14.
Alan I. Faden Thomas P. Jacobs George P. Smith Barth Green Justin A. Zivin 《Peptides》1983,4(5):631-634
The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that β-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its “anti-endorphin” actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-μ receptors. Dynorphin, an endogenous opioid with a high affinity for the κ receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at κ receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury. 相似文献
15.
Construction of a plasmid containing the complete coding region of human elongation factor 2. 总被引:3,自引:0,他引:3
A plasmid pUChEF-2 containing the coding sequence as well as the complete 3'-untranslated region (3'UTR) of human EF-2 mRNA was constructed. The plasmid construct was assembled from a cDNA insert of pHGR81 (Rapp et al., (1988) Biol. Chem. Hoppe-Seyler 369, 247-250) comprising the C-terminal portion of the coding region and the 3'UTR, as well as a polymer chain reaction PCR fragment (Rapp et al., (1989) Biol. Chem. Hoppe-Seyler 370, 1071-1075) covering the missing part of the coding region from the amino-terminus. 相似文献
16.
The cytotoxic and mutagenic effect of (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE) in normally excision diploid human cells treated just prior to onset of S was compared with that of cells allowed ~ 16 h for excision repair before onset of S and with that observed in excision-deficient serodema pigmentosum (SP12BE) cells. The cells were synchronized by release from density inhibition of cell replication. DNA synthesis began ~ 22 h after the cells were plated at lower density (i.e., 1.4 × 104 cells/cm2). The frequency of thioguanine-resistant mutants induced in normal cells treated just prior to onset of S was ~ 12- to 16-fold higher than that observed in cells treated in early G1 or treated in G0 (confluence) and then plated at lower density. The frequency approximated that expected for XP12BE cells from extrapolation of data obtained at lower doses. The frequency of mutants measured in normal cells treated in exponential growth was also much higher than that in the cells treated in early G1 or in G0, No such difference could be seen in XP12BE cells treated in exponential growth or in G0. In contrast to the mutagenicity data in the normal cells, there was no significant difference in the slope of the survival curve of normal cells treated at various times prior to S phase at low densities. However, normal cells treated even at the onset of S exhibited survival equal to XP12BE cells give a 4- to 5-fold lower dose. The data support the hypothesis that DNA synthesis is the cellular event which converts unexcised DNA lesions into mutations. However, they indicate that S is not the event primarily responsible for translating DNA damage into cell death. Accompanying studies on the rate of excision of anti BPDE adducts from the normal cells during the period priot to S support the conclusions. 相似文献
17.
Adenosine and the synthetic adenosine agonists 2-chloroadenosine and N6-(L-2-phenylisopropyl)-adenosine were tested for effects on hormone secretion from the rat isolated perfused pancreas. These nucleosides, at concentrations of 5 μM, markedly potentiated both phases of arginine-induced glucagon release; the two synthetic agonists were more effective than adenosine. In the absence of arginine, each of the nucleosides induced a transient burst of glucagon. In contrast, adenosine and both synthetic agonists inhibited arginine-induced insulin secretion to varying degrees and caused only negligible insulin release when perfused without arginine. The adenosine antagonist 8-(-sulfophenyl)-theophylline prevented the actions of adenosine on hormone release from the pancreas. Our data suggest that adenosine potentiation of arginine-induced glucagon release may be mediated via adenosine receptors on alpha cell membranes; such a mechanism could provide an important endogenous control over glucagon secretion. 相似文献
18.
19.
Wolf Heusermann Justin Hean Dominic Trojer Emmanuelle Steib Stefan von Bueren Alexandra Graff-Meyer Christel Genoud Katrin Martin Nicolas Pizzato Johannes Voshol David V. Morrissey Samir E.L. Andaloussi Matthew J. Wood Nicole C. Meisner-Kober 《The Journal of cell biology》2016,213(2):173-184
Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery. 相似文献
20.
Error‐free and mutagenic processing of topoisomerase 1‐provoked damage at genomic ribonucleotides 下载免费PDF全文
Genomic ribonucleotides incorporated during DNA replication are commonly repaired by RNase H2‐dependent ribonucleotide excision repair (RER). When RNase H2 is compromised, such as in Aicardi‐Goutières patients, genomic ribonucleotides either persist or are processed by DNA topoisomerase 1 (Top1) by either error‐free or mutagenic repair. Here, we present a biochemical analysis of these pathways. Top1 cleavage at genomic ribonucleotides can produce ribonucleoside‐2′,3′‐cyclic phosphate‐terminated nicks. Remarkably, this nick is rapidly reverted by Top1, thereby providing another opportunity for repair by RER. However, the 2′,3′‐cyclic phosphate‐terminated nick is also processed by Top1 incision, generally 2 nucleotides upstream of the nick, which produces a covalent Top1–DNA complex with a 2‐nucleotide gap. We show that these covalent complexes can be processed by proteolysis, followed by removal of the phospho‐peptide by Tdp1 and the 3′‐phosphate by Tpp1 to mediate error‐free repair. However, when the 2‐nucleotide gap is associated with a dinucleotide repeat sequence, sequence slippage re‐alignment followed by Top1‐mediated religation can occur which results in 2‐nucleotide deletion. The efficiency of deletion formation shows strong sequence‐context dependence. 相似文献