全文获取类型
收费全文 | 1366篇 |
免费 | 105篇 |
专业分类
1471篇 |
出版年
2022年 | 10篇 |
2021年 | 26篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 12篇 |
2017年 | 26篇 |
2016年 | 35篇 |
2015年 | 43篇 |
2014年 | 51篇 |
2013年 | 73篇 |
2012年 | 86篇 |
2011年 | 81篇 |
2010年 | 43篇 |
2009年 | 40篇 |
2008年 | 73篇 |
2007年 | 81篇 |
2006年 | 82篇 |
2005年 | 98篇 |
2004年 | 65篇 |
2003年 | 68篇 |
2002年 | 54篇 |
2001年 | 29篇 |
2000年 | 36篇 |
1999年 | 40篇 |
1998年 | 18篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 8篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 16篇 |
1989年 | 35篇 |
1988年 | 18篇 |
1987年 | 19篇 |
1986年 | 18篇 |
1985年 | 13篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1971年 | 3篇 |
排序方式: 共有1471条查询结果,搜索用时 0 毫秒
991.
Noguchi T Onodera A Tomisawa K Yamashita M Takeshita K Yokomori S 《Bioorganic & medicinal chemistry》2002,10(8):2713-2721
We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No significant difference has been observed between the two enantiomers. In a pre-clinical study of esonarimod, other metabolites were detected in rat blood or urine. We also synthesized these compounds as authentic samples to analyze the human metabolites in clinical studies of esonarimod. 相似文献
992.
993.
Kawano-Kawada M Iwaki T Hosaka T Murata T Yamato I Homma M Kakinuma Y 《Journal of bacteriology》2012,194(17):4546-4549
The crystal structures of the Na(+)- and Li(+)-bound NtpK rings of Enterococcus hirae V-ATPase have been obtained. The coupling ion (Na(+) or Li(+)) was surrounded by five oxygen atoms contributed by residues T64, Q65, Q110, E139, and L61, and the hydrogen bonds of the side chains of Q110, Y68, and T64 stabilized the position of the E139 γ carboxylate essential for ion occlusion (PDB accession numbers 2BL2 and 2CYD). We previously indicated that an NtpK mutant strain (E139D) lost tolerance to sodium but not to lithium at alkaline pHs and suggested that the E139 residue is indispensable for the enzymatic activity of E. hirae V-ATPase linked with the sodium tolerance of this bacterium. In this study, we examined the activities of V-ATPase in which these four residues, except for E139, were substituted. The V-ATPase activities of the Q65A and Y68A mutants were slightly retained, but those of the T64A and Q110A mutants were negligible. Among the residues, T64 and Q110 are indispensable for the ion coupling of E. hirae V-ATPase, in addition to the essential residue E139. 相似文献
994.
995.
996.
997.
Chorioptic mange in a wild Japanese serow 总被引:1,自引:0,他引:1
Shibata A Yachimori S Morita T Kanda E Ike K Imai S 《Journal of wildlife diseases》2003,39(2):437-440
Parasitologic and histopathologic examinations were performed on a wild Japanese serow (Capricornis crispus) with severe dermatitis from Tochigi, Japan in February 1999. The serow was infested with a large number Chorioptes bovis. Marked parakeratotic hyperkeratosis was characteristic of the lesions induced by these mites. Japanese serow is a new host of C. bovis. 相似文献
998.
A reliable method is reported for the long-term preservation of ovaries and spermatozoa of the silkworm (Bombyx mori). Three studies are presented. In the first, ovaries were removed from larvae at either 3rd, 4th, or 5th instar, cryopreserved, and stored in liquid nitrogen. Thawed ovaries were transplanted to surgically castrated female larvae at the same or a different developmental stage. The highest percentage of recipient females producing eggs resulted into either 3rd or 4th instar larvae (respectively, 22.1 and 8.7%). Similarly, the highest levels of other measurements of successful cryopreservation and transplanted ovary, and number of eggs laid, occurred with the same combination of donor and recipient developmental stages. Other combinations of ovary/recipient developmental stages yielded lower results. In the second experiment, semen was collected from male moths, cryopreserved, and then thawed semen was diluted with trypsin solution and artificially inseminated into females obtained from the best conditions of first experiment. A small percentage of inseminated moths laid eggs (8-10.3%) compared to that of controls (100%). In addition, the fertility of eggs from experimental moths was lower than that of control females (respectively, 40.3-88% and 97.5%). In the third experiment, eggs were surgically removed from ovarian tubules of moth following transplantation of thawed ovaries and subjected to parthenogenetic activation and artificial hatching. As expected, all resulting moths were female and, following natural mating or artificial insemination with thawed semen, yielded normal offspring at high rates. 相似文献
999.
Sumino H Ichikawa S Itoh H Utsugi T Ohyama Y Umeda M Nakamura T Kanda T Mizunuma H Tomono S Murakami M Kurabayashi M 《Hormone research》2003,60(3):134-142
OBJECTS: To investigate the effect of combined estrogen and progesterone therapy on insulin resistance (IR) and carbohydrate and lipid metabolism in postmenopausal women (PMW) with impaired (IGT) and normal glucose tolerance (NGT). METHODS: Sixteen Japanese PMW with IGT and 33 with NGT received daily oral hormone replacement therapy (HRT; 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate) for 12 months. As controls, 13 Japanese PMW with IGT and 31 with NGT were enrolled and not treated by HRT. Fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI), and IR were measured in each subject at study initiation and 12 months later. We used homeostasis model assessment (HOMA) to determine IR. RESULTS: FPG and HOMA IR were decreased in both HRT groups, and fasting IRI was reduced in the HRT-NGT group. In controls, FPG, fasting IRI, and HOMA IR were unaltered. Total and low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased in both HRT groups, but triglyceride was unchanged. In controls, lipid metabolism was unaltered. CONCLUSION: HRT decreased IR and improved carbohydrate and lipid metabolism in Japanese PMW with IGT and NGT. These beneficial effects argue for the use of HRT in PMW with IGT as well as NGT. 相似文献
1000.
Rer1p,a retrieval receptor for ER membrane proteins,recognizes transmembrane domains in multiple modes 下载免费PDF全文
The yeast Golgi membrane protein Rer1p is required for the retrieval of various endoplasmic reticulum (ER) membrane proteins such as Sec12p and Sec71p to the ER. We demonstrate here that the transmembrane domain (TMD) of Sec71p, a type-III membrane protein, contains an ER localization signal, which is required for physical recognition by Rer1p. The Sec71TMD-GFP fusion protein is efficiently retrieved to the ER by Rer1p. The structural feature of this TMD signal turns out to be the spatial location of polar residues flanking the highly hydrophobic core sequence but not the whole length of the TMD. On the Rer1p side, Tyr152 residue in the 4th TMD is important for the recognition of Sec12p but not Sec71p, suggesting that Rer1p interacts with its ligands at least in two modes. Sec71TMD-GFP expressed in the Deltarer1 mutant cells is mislocalized from the ER to the lumen of vacuoles via the multivesicular body (MVB) sorting pathway. In this case, not only the presence of polar residues in the Sec71TMD but also the length of the TMD is critical for the MVB sorting. Thus, the Rer1p-dependent ER retrieval and the MVB sorting in late endosomes both watch polar residues in the TMD but in a different manner. 相似文献