全文获取类型
收费全文 | 3705篇 |
免费 | 242篇 |
国内免费 | 206篇 |
专业分类
4153篇 |
出版年
2023年 | 55篇 |
2022年 | 85篇 |
2021年 | 107篇 |
2020年 | 107篇 |
2019年 | 138篇 |
2018年 | 125篇 |
2017年 | 80篇 |
2016年 | 114篇 |
2015年 | 121篇 |
2014年 | 198篇 |
2013年 | 266篇 |
2012年 | 165篇 |
2011年 | 232篇 |
2010年 | 171篇 |
2009年 | 210篇 |
2008年 | 233篇 |
2007年 | 229篇 |
2006年 | 173篇 |
2005年 | 151篇 |
2004年 | 130篇 |
2003年 | 128篇 |
2002年 | 107篇 |
2001年 | 46篇 |
2000年 | 54篇 |
1999年 | 47篇 |
1998年 | 45篇 |
1997年 | 38篇 |
1996年 | 30篇 |
1995年 | 29篇 |
1994年 | 23篇 |
1993年 | 15篇 |
1992年 | 16篇 |
1991年 | 13篇 |
1990年 | 15篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1986年 | 4篇 |
1985年 | 27篇 |
1984年 | 41篇 |
1983年 | 54篇 |
1982年 | 50篇 |
1981年 | 38篇 |
1980年 | 36篇 |
1979年 | 32篇 |
1978年 | 34篇 |
1977年 | 36篇 |
1976年 | 26篇 |
1975年 | 22篇 |
1974年 | 19篇 |
1973年 | 10篇 |
排序方式: 共有4153条查询结果,搜索用时 0 毫秒
111.
Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition 总被引:4,自引:0,他引:4
Lipid peroxidation in rat brain mitochondria was induced by NADH in the presence of ADP and FeCl3. CV-2619 inhibited the lipid peroxidation in a concentration-dependent manner; the concentration giving 50% inhibition (IC50) was 84 microM. In addition, the inhibitory effect of CV-2619 was strongly enhanced by adding substrates of mitochondrial respiration; when succinate, glutamate, or succinate plus glutamate was added, the IC50 of CV-2619 was changed to 1.1, 10, or 0.5 microM, respectively. Metabolites of CV-2619 also inhibited the lipid peroxidation. The inhibitory effect of CV-2619 on mitochondrial lipid peroxidation disappeared when TTFA, an inhibitor of complex II in mitochondrial respiratory chain, was added. The results indicate that in mitochondria CV-2619 is changed to its reduced form which inhibits lipid peroxidation. 相似文献
112.
T. Hashizume H. SaitoT. Sawada T. YaegashiA. Ahmed Ezzat K. SawaiT. Yamashita 《Animal reproduction science》2010
The aims of the present study were to clarify the effect of kisspeptin-10 (Kp10) on the secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and prolactin (PRL) in goats, and compare the characteristics of any response with those of the response to gonadotropin-releasing hormone (GnRH). The experiments were performed using four female goats (4–5 years old) in the luteal phase of estrous cycle. A single intravenous (i.v.) injection of 1, 5 and 10 μg/kg b.w. (0.77, 3.85 and 7.69 nmol/kg b.w.) of Kp10 stimulated the release of LH. Maximum values were observed 20–30 min after the injection. On the other hand, Kp10 did not alter plasma GH and PRL concentrations significantly. Three consecutive i.v. injections of Kp10 (5 μg/kg b.w.) or GnRH (5 μg/kg b.w.: 4.23 nmol/kg b.w.) at 2-h intervals increased both plasma LH and FSH levels after each injection (P < 0.05); however, the responses to Kp10 were different from a similar level of GnRH. The rate of decrease in LH and FSH levels following the peak was attenuated in Kp10-treated compared to GnRH-treated animals. These results show that Kp10 can stimulate the release of LH and FSH but not GH and PRL in female goats and suggest that the LH- and FSH-releasing effect of the i.v. injection of Kp10 is less potent than that of GnRH. 相似文献
113.
Recombinant Mycobacterium sp. strain MR65 carrying dszABCD genes was used for desulfurization of 10-methylbenzo[b]naphtho[2,1-d]thiophene (10-methyl BNT) in the hexadecane phase. The specific activity was 25% of that of dibenzothiophene (DBT). One of two major metabolites of 10-methyl BNT produced by strain MR65 was identified as 1-methoxy-2-(3-methylphenyl)naphthalene by 1H and 13C NMR. The other major metabolite and two minor metabolites were determined as 1-hydroxy-2-(3-methylphenyl)naphthalene, 2-(2-methoxy-3-methylphenyl)naphthalene and 2-(2-hydroxy-3-methylphenyl)naphthalene, respectively, by HPLC and GC-MS. The production ratio of the two desulfurization metabolite isomers was 0.99:0.01, calculated on the basis of peak GC areas. These results indicated that the C-S bond adjacent to the naphthalene skeleton was selectively cleaved to form the two major compounds. 相似文献
114.
A pair of stereoisomeric covalent adducts to guanine in double-stranded DNA, derived from the reaction of mutagenic and tumorigenic metabolites of benzo[a]pyrene, have been well characterized structurally and thermodynamically. Both high-resolution NMR solution structures and an array of thermodynamic data are available for these 10S (+)- and 10R (-)-trans-anti -[BP]-N(2)-dG adducts in double-stranded deoxyoligonucleotides. The availability of experimentally well-characterized duplexes containing these two stereoisomeric guanine adducts provides an opportunity for evaluating the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for computing thermodynamic properties from molecular dynamics ensembles. We have carried out 3-ns molecular dynamics simulations, using NMR solution structures as the starting models for the 10S (+)- and 10R (-)-trans-anti-dG adducts in a DNA duplex 11-mer using AMBER 6.0. We employed the MM-PBSA method to compute the free energies, enthalpies, and entropies of the two adducts. Our complete thermodynamic analysis agrees quite well with the full experimental thermodynamic characterization of these adducts, showing essentially equal stabilities of the two adducts. We also calculated the nuclear Overhauser effect (NOE) distances from the molecular dynamics trajectories, and compared them against the experimental NMR-derived NOE distances. Our results showed that the simulated structures are in good agreement with the NMR experimental NOE data. Furthermore, the molecular dynamics simulations provided new structural and biological insights. Specifically, the puzzling observation that the BP aromatic ring system in the 10S (+)-trans-anti-dG adduct is more exposed to the aqueous solvent than the 10R (-)-trans-anti-dG adduct, is rationalized in terms of the adduct structures. The structural and thermodynamic features of these stereoisomeric adducts are also discussed in relation to their reported low susceptibilities to nucleotide excision repair. 相似文献
115.
Incubation studies have been carried out using normal breast tissue and breast tissue from patients with gynecomastia, mammary dysplasia and breast carcinoma to determine the pattern of androstenedione metabolism. All tissues formed estrone (E1) and testosterone (T) in all incubations. Estradiol (E2) was isolated in incubations of tissue from 1 to 6 patients with mammary dysplasia, 5 of 6 patients with gynecomastia and in all incubations with normal and carcinoma tissue. Estrone formation was lowest in mammary dysplasia and gynecomastia, and higher in apparently normal breast tissue. The greatest E1 formation was found in incubations with breast carcinoma tissue, although there was considerable variation within this tissue group. Estradiol formation was low in all tissues, with the highest conversion rates in carcinoma tissue. Testosterone formation in carcinoma tissue was greater than in mammary dysplasia or gynecomastia, but similar to apparently normal tissue. These results indicate that breast tissue from different pathological states varies in its capacity to aromatize androstenedione (A) to estrogenic products and to convert it to other androgens. They have also shown that the pattern of metabolism is distinctive for the nature of the pathological abnormality. 相似文献
116.
Nucleosomal arrays self‐assemble into supramolecular globular structures lacking 30‐nm fibers 下载免费PDF全文
Sachiko Tamura Yasumasa Joti Takaaki Hikima Heather Szerlong Christine Krause Jake Herman Erik Seidel Jennifer DeLuca Tetsuya Ishikawa Jeffrey C Hansen 《The EMBO journal》2016,35(10):1115-1132
The existence of a 30‐nm fiber as a basic folding unit for DNA packaging has remained a topic of active discussion. Here, we characterize the supramolecular structures formed by reversible Mg2+‐dependent self‐association of linear 12‐mer nucleosomal arrays using microscopy and physicochemical approaches. These reconstituted chromatin structures, which we call “oligomers”, are globular throughout all stages of cooperative assembly and range in size from ~50 nm to a maximum diameter of ~1,000 nm. The nucleosomal arrays were packaged within the oligomers as interdigitated 10‐nm fibers, rather than folded 30‐nm structures. Linker DNA was freely accessible to micrococcal nuclease, although the oligomers remained partially intact after linker DNA digestion. The organization of chromosomal fibers in human nuclei in situ was stabilized by 1 mM MgCl2, but became disrupted in the absence of MgCl2, conditions that also dissociated the oligomers in vitro. These results indicate that a 10‐nm array of nucleosomes has the intrinsic ability to self‐assemble into large chromatin globules stabilized by nucleosome–nucleosome interactions, and suggest that the oligomers are a good in vitro model for investigating the structure and organization of interphase chromosomes. 相似文献
117.
118.
The objective of this study was to determine the upper thermal limits of Arctic cod Boreogadus saida by measuring the response of maximum heart rate (fHmax) to acute warming. One set of fish were tested in a field laboratory in Cambridge Bay (CB), Nunavut (north of the Arctic Circle), and a second set were tested after air transport to and 6 month temperature acclimation at the Vancouver Aquarium (VA) laboratory. In both sets of tests, with B. saida acclimated to 0° C, fHmax increased during acute warming up to temperatures considerably higher than the acclimation temperature and the near‐freezing Arctic temperatures in which they are routinely found. Indeed, fHmax increased steadily between 0·5 and 5·5° C, with no significant difference between the CB and VA tests (P > 0·05) and with an overall mean ± s.e. Q10 of 2·4 ± 0·5. The first Arrhenius breakpoint temperature (TAB) for fHmax was also statistically indistinguishable for the two sets of tests (mean ± s.e. 3·2 ± 0·3 and 3·6 ± 0·3° C), suggesting that the temperature optimum for B. saida could be reliably measured after live transport to a more southerly laboratory location. Continued warming above 5·5° C revealed a large variability among individuals in the upper thermal limits that triggered cardiac arrhythmia (Tarr), ranging from 10·2 to 15·2° C with mean ± s.e. 12·4 ± 0·4° C (n = 11) for the field study. A difference did exist between the CB and VA breakpoint temperatures when the Q10 value decreased below 2 (the Q10 breakpoint temperature; TQB) at 8·0 and 5·5° C, respectively. These results suggest that factors, other than thermal tolerance and associated cardiac performance, may influence the realized distribution of B. saida within the Arctic Circle. 相似文献
119.
Akira Inoue Naoki Yamamoto Masatsugu Kimura Koji Nishio Hideo Yamane Koichi Nakajima 《FEBS letters》2014
RBM10, originally called S1-1, is a nuclear RNA-binding protein with domains characteristic of RNA processing proteins. It has been reported that RBM10 constitutes spliceosome complexes and that RBM5, a close homologue of RBM10, regulates alternative splicing of apoptosis-related genes, Fas and cFLIP. In this study, we examined whether RBM10 has a regulatory function in splicing similar to RBM5, and determined that it indeed regulates alternative splicing of Fas and Bcl-x genes. RBM10 promotes exon skipping of Fas pre-mRNA as well as selection of an internal 5′-splice site in Bcl-x pre-mRNA. We propose a consensus RBM10-binding sequence at 5′-splice sites of target exons and a mechanistic model of RBM10 action in the alternative splicing. 相似文献
120.
Carlos Albuquerque Francisco Morinha João Requicha Isabel Dias Henrique Guedes-Pinto Carlos Viegas Estela Bastos 《Gene》2014
Periodontal disease (PD) refers to a group of inflammatory diseases that affect the periodontium, the organ which surrounds and supports the teeth. PD is a highly prevalent disease with a multifactorial etiology and, in humans the individual susceptibility is known to be strongly determined by genetic factors. Several candidate genes have been studied, namely genes related with molecules involved in the inflammatory response. Interleukin-10 (IL-10) is a cytokine with important anti-inflammatory and immunomodulatory roles, and several studies indicate an association between IL10 polymorphisms and PD. In dogs, an important animal model in periodontology, PD is also a highly prevalent naturally occurring disease, and only now are emerging the first studies evaluating the genetic predisposition. In this case–control study, a population of 90 dogs (40 dogs with PD and 50 healthy dogs) was used to study the IL10 gene, and seven new genetic variations in this gene were identified. No statistically significant differences were detected in genotype and allele frequencies of these variations between the PD cases and control groups. Nevertheless, one of the variations (IL10/2_g.285G > A) leads to an amino acid change (glycine to arginine) in the putative signal peptide, being predicted a potential influence on IL-10 protein functionality. Further investigations are important to clarify the biological importance of these new findings. The knowledge of these genetic determinants can help to understand properly the complex causal pathways of PD, with important clinical implications. 相似文献