全文获取类型
收费全文 | 15327篇 |
免费 | 1630篇 |
国内免费 | 2658篇 |
出版年
2024年 | 63篇 |
2023年 | 289篇 |
2022年 | 558篇 |
2021年 | 790篇 |
2020年 | 590篇 |
2019年 | 798篇 |
2018年 | 712篇 |
2017年 | 596篇 |
2016年 | 742篇 |
2015年 | 1008篇 |
2014年 | 1212篇 |
2013年 | 1256篇 |
2012年 | 1518篇 |
2011年 | 1390篇 |
2010年 | 915篇 |
2009年 | 833篇 |
2008年 | 943篇 |
2007年 | 823篇 |
2006年 | 763篇 |
2005年 | 642篇 |
2004年 | 549篇 |
2003年 | 493篇 |
2002年 | 433篇 |
2001年 | 302篇 |
2000年 | 235篇 |
1999年 | 196篇 |
1998年 | 141篇 |
1997年 | 117篇 |
1996年 | 91篇 |
1995年 | 58篇 |
1994年 | 58篇 |
1993年 | 41篇 |
1992年 | 65篇 |
1991年 | 54篇 |
1990年 | 58篇 |
1989年 | 36篇 |
1988年 | 25篇 |
1987年 | 26篇 |
1986年 | 31篇 |
1985年 | 20篇 |
1984年 | 20篇 |
1983年 | 22篇 |
1982年 | 15篇 |
1981年 | 15篇 |
1980年 | 8篇 |
1979年 | 17篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
11.
Z Z Chen G P Schwartz L Zong G T Burke J D Chanley P G Katsoyannis 《Biochemistry》1988,27(16):6105-6111
A two-chain, disulfide linked, insulin-like compound embodying the A-domain of insulin-like growth factor I (IGF-I) and the B-chain of insulin has been synthesized and characterized with respect to insulin-like biological activity and growth-promoting potency. The compound displays a potency of ca. 41% relative to insulin in assays for insulin-like activity (e.g., lipogenesis) but significantly higher activity than insulin, ca. 730% relative to insulin, in growth factor assays (e.g., thymidine incorporation). The compound is, however, a less potent growth factor than IGF-I itself, ca. 26.5% relative to IGF-I, and is not recognized by IGF carrier proteins. We conclude that structural features contained in the A-domain of IGF-I are primarily responsible for the growth-promoting ability displayed by IGF-I, while features in the B-domain are responsible for recognition by IGF carrier proteins. 相似文献
12.
Toxin–antitoxin (TA) systems are small genetic elements that typically encode a stable toxin and its labile antitoxin. These cognate pairs are abundant in prokaryotes and have been shown to regulate various cellular functions. Vibrio cholerae, a human pathogen that is the causative agent of cholera, harbors at least thirteen TA loci. While functional HigBA, ParDE have been shown to stabilize plasmids and Phd/Doc to mediate cell death in V. cholerae, the function of seven RelBE-family TA systems is not understood. In this study we investigated the function of the RelBE TA systems in V. cholerae physiology and found that six of the seven relBE loci encoded functional toxins in E. coli. Deletion analyses of each relBE locus indicate that RelBE systems are involved in biofilm formation and reactive oxygen species (ROS) resistance. Interestingly, all seven relBE loci are induced under the standard virulence induction conditions and two of the relBE mutants displayed a colonization defect, which was not due to an effect on virulence gene expression. Although further studies are needed to characterize the mechanism of action, our study reveals that RelBE systems are important for V. cholerae physiology. 相似文献
13.
14.
15.
我国某些常见化石硅藻的环境分析 总被引:6,自引:0,他引:6
蒋辉 《Acta Botanica Sinica》1987,(4)
本文详细研究了中国海表层沉积物中的常见化石硅藻,结果表明,这些种的分布范围及数量变化随环境的不同而变化。因此,根据柱状样品中这些种类数量的变化,能够推断古气候变化,恢复古地理环境,再现海平面波动历程,进而划分、对比第四系地层。 相似文献
16.
四川盐源盆地哺乳类化石及其意义 总被引:5,自引:0,他引:5
本文简述盐源盆地上新世和更新世晚期两个不同时代的哺乳动物化石十余种,据之修正了该盆地晚新生代沉积的时代和对比关系. 相似文献
17.
Harringtonine showed cross resistance in adriamycin-resistant murine leukemia P388 (P388/ADM) and human leukemia K562 (K562/ADM) cells. The relative resistance of the P388/ADM and K562/ADM cells to harringtonine was about 7 and 40, respectively. Calcium influx blockers, diltiazem and the biscoclaurine alkaloid cepharanthine enhanced the cytotoxicity of harringtonine in P388/ADM and K562/ADM cells. The extent of enhancement was different for the two drugs, and up to a 9- to 10-fold increase in harringtonine cytotoxicity occurred in P388/ADM cells, and 14- to 22-fold enhancement in K562/ADM cells with diltiazem or cepharanthine. Harringtonine resistance of P388/ADM was circumvented completely, and the resistance of K562/ADM was circumvented partially, by diltiazem or cepharanthine. The mechanism of enhanced cytotoxicity by diltiazem and cepharanthine is probably inhibition of active efflux of harringtonine in P388/ADM and K562/ADM cells. 相似文献
18.
Modelling basic features of specificity in the binding of a dicationic steroid diamine to double-stranded oligonucleotides.
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
An investigation of the intrinsically preferred binding modes of a steroid diamine, dipyrandium, to the double-stranded hexanucleotides d(TATATA)2, d(ATATAT)2, and d(CGCGCG)2 is carried out by the energy minimization procedure JUMNA. Several alternative binding modes are compared: groove binding in which the conformation of the oligonucleotide remains close to that of B-DNA, intercalation between base-pairs and interaction with variously kinked structures in which base pairs of dinucleoside steps open towards the groove in which the binding occurs. The favored binding configuration occurs at the d(TpA) step of the AT kinked nucleotides in which the kink opens the base pairs towards the minor groove. Thus, for the d(T1A2T3A4T5A6)2 sequences the preferred complexation involves the kink at the T3A4 step facing the cyclohexane rings A, B, and C of the ligand. For the d(A1T2A3T4A5T6)2 sequence, the kink occurs at the T2A3 step facing the cationic pyrrolidine ring linked to ring A. The binding of dipyrandium to d(CGCGCG)2 is found to be considerably less favourable than for either of the two (AT) sequences. 相似文献
19.
20.
We have investigated the effects of clinically available calcium channel blockers (nifedipine, verapamil and diltiazem) on isoproterenol stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) generation in intact human lymphocytes. After preincubation of various calcium antagonists with intact lymphocytes at 37 degrees C for 15 minutes, 10 microM nifedipine or verapamil partially inhibited isoproterenol induced cyclic AMP generation in the presence of cyclic AMP phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) while they alone had no effect on cyclic AMP level at a concentration of up to 100 microM. In contrast, 10 nM-1.0 microM nifedipine, verapamil or diltiazem potentiated cyclic AMP generation induced by isoproterenol in a dose dependent manner. Similar results were observed in the time course studies of cyclic AMP generation. These effects are somewhat similar to the effect of phenothiazine, a calmodulin inhibitor, which, at 10 microM (close to IC50), also potentiated the effects of isoproterenol. In contrast, lanthanum chloride (LaCl3), an extracellular inorganic calcium antagonist, at 1.0 mM, inhibited isoproterenol induced cyclic AMP generation. The biochemical mechanisms underlying these potentiating effects are unknown. It may be partly related to the effect of calcium channel blockers (at least for nifedipine) on preventing beta 2 adrenergic receptor desensitization. This may provide a potential mechanism for the synergistic effect between calcium channel blockers and beta 2 adrenoceptor agonists on bronchial dilatation. 相似文献