全文获取类型
收费全文 | 35401篇 |
免费 | 16230篇 |
国内免费 | 5篇 |
出版年
2023年 | 61篇 |
2022年 | 232篇 |
2021年 | 646篇 |
2020年 | 2311篇 |
2019年 | 3892篇 |
2018年 | 4041篇 |
2017年 | 4296篇 |
2016年 | 4371篇 |
2015年 | 4509篇 |
2014年 | 4195篇 |
2013年 | 4791篇 |
2012年 | 2662篇 |
2011年 | 2294篇 |
2010年 | 3572篇 |
2009年 | 2252篇 |
2008年 | 1288篇 |
2007年 | 940篇 |
2006年 | 876篇 |
2005年 | 809篇 |
2004年 | 788篇 |
2003年 | 680篇 |
2002年 | 661篇 |
2001年 | 319篇 |
2000年 | 241篇 |
1999年 | 206篇 |
1998年 | 100篇 |
1997年 | 77篇 |
1996年 | 63篇 |
1995年 | 66篇 |
1994年 | 38篇 |
1993年 | 55篇 |
1992年 | 38篇 |
1991年 | 37篇 |
1990年 | 19篇 |
1989年 | 16篇 |
1988年 | 16篇 |
1987年 | 9篇 |
1986年 | 14篇 |
1985年 | 19篇 |
1984年 | 16篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 11篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1977年 | 9篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1971年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 312 毫秒
141.
142.
Densely methylated DNA islands in mammalian chromosomal replication origins. 总被引:6,自引:3,他引:3 下载免费PDF全文
Densely methylated DNA sequence islands, designated DMIs, have been observed in two Chinese hamster cell chromosomal replication origins by using a PCR-based chemical method of detection. One of the origins, oriS14, is located within or adjacent to the coding sequence for ribosomal protein S14 on chromosome 2q, and the other, ori-beta, is approximately 17 kbp downstream of the dhfr (dihydrofolic acid reductase) locus on chromosome 2p. The DMI in oriS14 is 127 bp long, and the DMI in ori-beta is 516 bp long. Both DMIs are bilaterally methylated (i.e., all dCs are modified to 5-methyl dC) only in cells that are replicating their DNA. When cell growth and DNA replication are arrested, methylation of CpA, CpT, and CpC dinucleotides is lost and the sequence islands display only a subset of their originally methylated CpG dinucleotides. Several possible roles for DMI-mediated regulation of mammalian chromosomal origins are considered. 相似文献
143.
Elena Kosenko Yuri Kaminsky Eugenio Grau María-Dolores Miñana Goizane Marcaida Santiago Grisolía Vicente Felipo 《Journal of neurochemistry》1994,63(6):2172-2178
Abstract: Injection of large doses of ammonia into rats leads to depletion of brain ATP. However, the molecular mechanism leading to ATP depletion is not clear. The aim of the present work was to assess whether ammonium-induced depletion of ATP is mediated by activation of the NMDA receptor. It is shown that injection of MK-801, an antagonist of the NMDA receptor, prevented ammonia-induced ATP depletion but did not prevent changes in glutamine, glutamate, glycogen, glucose, and ketone bodies. Ammonia injection increased Na+ ,K+ -ATPase activity by 76%. This increase was also prevented by previous injection of MK-801. The molecular mechanism leading to activation of the ATPase was further studied. Na+ ,K+ -ATPase activity in samples from ammonia-injected rats was normalized by "in vitro" incubation with phorbol 12-myristate 13-acetate, an activator of protein kinase C. The results obtained suggest that ammonia-induced ATP depletion is mediated by activation of the NMDA receptor, which results in decreased protein kinase C-mediated phosphorylation of Na+ ,K+ -ATPase and, therefore, increased activity of the ATPase and increased consumption of ATP. 相似文献
144.
Induction of Nitric Oxide Synthase in Rat C6 Glioma Cells 总被引:9,自引:1,他引:8
Douglas L. Feinstein Elena Galea Steven Roberts Henrik Berquist Hong Wang Donald J. Reis 《Journal of neurochemistry》1994,62(1):315-321
Abstract: We have examined the induction of nitric oxide syhthase (NOS) activity in the rat astrocyte-derived C6 glioma cell line. In contrast to the previous results with primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin lipopolysaccharide (LPS; 1 μg/ml for 24 h) did not stimulate NO2 production. However, addition of either tumor necrosis factor-a (TNF-α) or interferon-γ (IFN-γ), cytokines that by themselves had no effect on NOS activity, imparted LPS responsiveness onto these cells in a dose-dependent manner (EC50 values of 39 ng/ml of TNF-α and 9.4 U/ml of IFN-γ), and the effect of TNF-α could be further potentiated (twofold) by the presence of interleukin-1β. The simultaneous presence of TNF-α and IFN-γ yielded a greater response than either cytokine alone; however, the respective EC50 values were not affected. A cytoplasmic extract from induced C6 cells catalyzed the Ca2+ -independent conversion of l -arginine to l - citrulline, with an apparent K m of 51.2 n M , and this activity could be blocked by l -arginine analogues in the potency order amino > methyl > nitroarginine. Immunoblot analysis revealed an apparent molecular mass of 125 kDa for the NOS protein induced in C6 cells. These results indicate that the combination of LPS plus cytokines can induce NOS activity in C6 glioma cells with properties similar to those of the enzyme expressed in primary astrocyte cultures. 相似文献
145.
Elena Albertazzi Rosanna Cardillo Stefano Servi Gioia Zucchi 《Biotechnology letters》1994,16(5):491-496
Summary 2-Phenylethanol and 2-phenylethylacetate important aroma components are obtained in substantial amounts whenHansenula anomala CBS 110 andKloeckera saturnus CBS 5761 are grown with L-phenylalanine as sole nitrogen source. Up to 2 g/L of mixtures of alcohol and ester are obtained. While in the first microorganism the alcohol predominates, in the second the acetate is formed almost exclusively. Experiments with 1-13C-d-Glucose show complete incorporation of the label into the methyl group of the acetate. 相似文献
146.
Valery Kukharenko Svetlana Sheleg Mikhail Freudine Elena Pichugina Alexander Delvig 《Human genetics》1994,94(1):80-82
Synthesis of glycosaminoglycans (GAGS) by fibroblasts derived from seven patients with Down's syndrome, five patients with Edwards' syndrome, and two patients with Patau's syndrome were studied in cell culture. The aneuploid strains were compared with diploid fibroblasts from age-matched controls. In terms of hyaluronic acid and sulfated GAG synthesis, the amount of synthesized hyaluronic acid was not significantly different between postnatal aneuploid strains and controls. 相似文献
147.
Daniele Morelli Alessandro Sardini Elena Villa Maria Luisa Villa Sylvie Ménard Maria I. Colnaghi Andrea Balsari 《Cancer immunology, immunotherapy : CII》1994,38(3):171-177
A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which recognizes both the epidermal growth factor receptor (EGF-R) and the drug doxorubicin, was produced by somatic hybridization of two hybridomas. The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time an antidotal effect on cells that did not overexpress the EGF-R. Distribution studies in mice indicate that the bsmAb selectively delivers the drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intestine, which is the main target of early anthracycline toxicity. In keeping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubiein, which is proved by retardation in loss of body weight and mortality. The effectiveness on tumour growth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a remarkable antidotal activity. 相似文献
148.
Escherichia coli grown anaerobically for osmotic studies upon increased osmolarity in alkaline medium carried out H+–K+-exchange in two steps, the first of which was DCCD1 sensitive and osmo-dependent and had the 2H+/K+ stoichiometry. H+-efflux in the presence of protonophore (CCCP) upon increase of osmolarity was shown to be high and inhibited by DCCD, whereas H+-efflux induced by a decrease of osmolarity was small and not inhibited by DCCD. The 2H+/K+-exchange was absent intrkA anduncA mutants. InuncB mutant 2H+/K+-exchange was not DCCD-and osmosensitive. Competition between DCCD and osmoshock on inhibition of 2H+/K+-exchange was found. Osmosensitivity of this exchange disappeared in spheroplasts. Osmosensitivity of both 2H+/K+-exchange and the F0F1 and osmoregulation of the F0F1 via F0 and a periplasmic space are postulated.Abbreviations F0F1
H+-ATPase complex
- F0
H+-channel, proteolipid
- F1
H+-ATPase
-
Trk
constitutive system for K+ uptake
- PV
periplasmic protein valve
- DCCD
N,N-dicyclohexylcarbodiimide
- CCCP
carbonylcyanide-m-chlorophenylhydrazone
- H or K
transmembrane electrochemical gradient for H+ or K+ respectively
-
membrane potential
- upshock or downshock
increase or decrease of medium osmolarity, respectively
- CGSC
E. coli Genetic Stock Center, Yale University, USA 相似文献
149.
Elena P. Sawin Laurence R. Harris Ana R. Campos Marla B. Sokolowski 《Journal of Insect Behavior》1994,7(4):553-567
In this paper we examine theDrosophila melanogaster larval response to light. We survey the morphology of the larval visual and motor systems in relation to larval locomotory behavior and phototaxis. In addition, this paper proposes a model of sensorimotor transformation and examines the reversal in taxis occurring at theD. melanogaster larval wnadering stage. 相似文献
150.
Elena P. Sawin Harold B. Dowse Melanie J. Hamblen-Coyle Jeffery C. Hall Marla B. Sokolowski 《Journal of Insect Behavior》1994,7(3):249-262
We examined the locomotor activity ofDrosophila melanogaster for the existence of circadian rhythms, using the wild type and two mutants of theperiod (per) gene,per
o andper
s. This was accomplished using a newly described apparatus for the recording and measurement of larval path lengths over a 96-h test period. None of the larvae examined exhibited appreciable diel rhythms under cycling conditions of light or temperature. Larvae were also not rhythmic under free-running conditions. Our results suggest that theper gene does not influence an observable locomotor behavioral phenotype in the larval stage of development. 相似文献