全文获取类型
收费全文 | 2239篇 |
免费 | 104篇 |
专业分类
2343篇 |
出版年
2023年 | 4篇 |
2022年 | 16篇 |
2021年 | 25篇 |
2020年 | 9篇 |
2019年 | 14篇 |
2018年 | 33篇 |
2017年 | 20篇 |
2016年 | 44篇 |
2015年 | 80篇 |
2014年 | 79篇 |
2013年 | 126篇 |
2012年 | 147篇 |
2011年 | 155篇 |
2010年 | 95篇 |
2009年 | 95篇 |
2008年 | 161篇 |
2007年 | 153篇 |
2006年 | 144篇 |
2005年 | 153篇 |
2004年 | 142篇 |
2003年 | 145篇 |
2002年 | 127篇 |
2001年 | 30篇 |
2000年 | 23篇 |
1999年 | 29篇 |
1998年 | 29篇 |
1997年 | 28篇 |
1996年 | 28篇 |
1995年 | 33篇 |
1994年 | 11篇 |
1993年 | 19篇 |
1992年 | 23篇 |
1991年 | 12篇 |
1990年 | 13篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 3篇 |
排序方式: 共有2343条查询结果,搜索用时 0 毫秒
71.
Kensuke Kobayashi Minaho Uchiyama Hirobumi Takahashi Hiroshi Kawamoto Satoru Ito Takashi Yoshizumi Hiroshi Nakashima Tetsuya Kato Atsushi Shimizu Izumi Yamamoto Masanori Asai Hiroshi Miyazoe Akio Ohno Mioko Hirayama Satoshi Ozaki Takeshi Tani Yasuyuki Ishii Takeshi Tanaka Takanobu Mochidome Kiyoshi Tadano Osamu Okamoto 《Bioorganic & medicinal chemistry letters》2009,19(11):3096-3099
The synthesis and biological evaluation of new potent opioid receptor-like 1 (ORL1) antagonists are presented. Conversion of the thioether linkage of the prototype [It is reported prior to this communication as a consecutive series.: Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.; Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto, O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited potent ORL1 activity, excellent selectivity over other receptors and ion channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a clinical candidate for a brain-penetrable ORL1 antagonist. 相似文献
72.
Yoshiaki?KaiEmail author Tomoyasu?Sato Masanori?Nakae Tetsuji?Nakabo Yoshihiko?Machida 《Ichthyological Research》2004,51(4):381-385
The anterior half of the mitochondrial DNA control region (mtCR) sequence (ca. 400 base pairs) was compared between two color morphotypes (A, B) of Parapercis sexfasciata from Tosa Bay, southern Japan, using 16 and 21 specimens, respectively. Intramorphotypic mtCR divergences were only 0.0–0.5% and 1.0–2.5% for morphotypes A and B, respectively. In contrast, intermorphotypic mtCR divergence was much greater, 12.7–14.0%. Furthermore, phylogenetic analysis using a neighbor-joining algorithm, with P. multifasciata as an outgroup, showed that each morphotype was reciprocally monophyletic. These results and the distinct coloration and overlapping distribution indicate that the two color morphotypes of P. sexfasciata represent two distinct species. Mismatch distribution analysis suggested that both morphotypes had undergone population expansion; however, estimates of initial population sizes and mutational timescales suggested that morphotype B comprises historically larger and older populations than morphotype A. 相似文献
73.
Shinobu Sato Masanori Kanazawa Kosuke Mukumoto Michinori Waki 《Analytical biochemistry》2008,381(2):233-239
A thiolated oligonucleotide having three ferrocenes was immobilized on a gold electrode through the sulfur-gold linkage. This electrode showed a current response based on the redox reaction of the ferrocene moieties and this response was decreased after treatment with deoxyribonuclease I (DNase I), suggesting the disappearance of the ferrocene moieties on the electrode by the DNase I digestion. A linear correlation between i0 and i, which are current peaks before and after DNase I treatment, respectively, was observed and this slope was decreased with increase in the amount of DNase I. No current decrease was observed in the presence of EDTA or RNase A instead of DNase I. These results suggested that the current decrease responded specifically to the amount of DNase I and this electrode could be used for an electrochemical DNase I assay. Under the optimum conditions of DNase I digestion at 37 °C for 30 min, a quantitative analysis could be achieved in the range of 10−4-10−2 units/μl of DNase I. 相似文献
74.
Protoplasts derived from tissue-cultured shoot primordia of garlic (Allium sativum L.) initiated successive cell divisions within 4 days and formed small individual calli (0.2mm in diameter) after 5 weeks of culture on Gamborg's B5 medium supplemented with 0.1% casein hydrolysate, 1mg/1 1-naphthaleneacetic acid and 1mg/1 6-benzylaminopurine. Plating efficiency was roughly 5% at the density of 1x104 protoplasts/ml of medium. Adventitious buds developed from the calli during subsequent subculture on Gamborg's B5 medium supplemented with 40mg/l adenine and 10% coconut milk. When transferred to the same medium without supplements, these buds grew into shoots and rooted. The regenerated garlic plantlets were successfully transferred to the greenhouse and grew into whole plants. 相似文献
75.
The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4(+) T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4(+) T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who had ex vivo gamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4(+) T cells, which are cross-reactive to both influenza A and B viruses. 相似文献
76.
Ohashi S Nishio A Nakamura H Kido M Ueno S Uza N Inoue S Kitamura H Kiriya K Asada M Tamaki H Matsuura M Kawasaki K Fukui T Watanabe N Nakase H Yodoi J Okazaki K Chiba T 《American journal of physiology. Gastrointestinal and liver physiology》2006,290(4):G772-G781
Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis. 相似文献
77.
Facile enzymatic conversion of lactose into lacto-N-tetraose and lacto-N-neotetraose 总被引:1,自引:0,他引:1
Lacto-N-tetraose (Galbeta1 -3GlcNAcbeta1-3Galbeta1-4Glc, LNT) and lacto-N-neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc, LNnT) were enzymatically synthesized by consecutive additions of GlcNAc and Gal residues to lactose. Lacto-N-triose II (GlcNAcbeta1-3Galbeta1-4Glc) was prepared first by the transfer of GlcNAc from UDP-GlcNAc to lactose by beta-1,3-N-acetylglucosaminyltransferase from bovine serum. The resulting lacto-N-triose II was converted into LNT and LNnT utilizing two kinds of beta-D-galactosidase-mediated transglycosylations. Thus, beta-D-galactosidase from Bacillus circulans ATCC31382 induced regioselective galactosyl transfer from o-nitrophenyl beta-D-galactoside to the OH-3" position of lacto-N-triose II, and commercially available beta-D-galactosidase from B. circulans to the OH-4" position of lacto-N-triose II. These convenient processes are suitable for large-scale preparations of LNT and LNnT. As another method, LNT was directly synthesized from lactose as an initial substance, utilizing lacto-N-biosidase (Aureobacterium sp. L-101)-mediated transglycosylation with Galbeta1-3GlcNAcbeta-pNP donor. 相似文献
78.
Kentaro?HayashiEmail author Masanori?Okazaki Norihiro?Itsubo Atsushi?Inaba 《The International Journal of Life Cycle Assessment》2004,9(1):13-22
Background Acidification is one of the important impact categories for life cycle impact assessment. Although its characterization has
progressed during this decade through the employment of midpoint approaches, only limited studies of endpoint approaches have
been performed. Objective. This study aimed at developing damage function of acidification for terrestrial ecosystems in Japan.
Damage function expresses a quantitative relationship between the inventory and endpoint damage.
Methods The geographical boundary was limited in Japan both for emission and impact. In this study, sulfur dioxide (SO2), nitrogen monoxide (NO), nitrogen dioxide (NO2) (NO and NO2 collectively mean NOx), hydrogen chloride (HC1), and ammonia (NH3) were considered as major causative substances of acidification. Net primary production (NPP) of existing vegetation was
adopted as an impact indicator of terrestrial ecosystems. The aluminum toxicity was adopted as the major factor of effect
on terrestrial ecosystems due to acidification. The leachate concentration of monomeric inorganic aluminum ions was selected
to express the plant toxicity of aluminum.
Results and Discussion The results of damage function gave utilizable factors both for a midpoint approach and an endpoint approach; Atmospheric
Deposition Factor (ADF) and Damage Factor (DF) applicable to the former and the latter, respectively. The ADF indicates an
increase of H+ deposition per unit area to an additional emission of causative sustance. The additional emission corresponds to some alternatives
in industry, not the baseline emission. The DF indicates the total NPP damage in all of Japan due to the additional emission
of causative substances. The derived NPP damage is on the order of one millionth of the NPP itself. HC1 and NH3 showed larger
ADFs and DFs than that of SO2 and NOx. The reason was ascribed to the relatively large source-receptor relationships (SRR) of HC1 and NH3. However, since the method applied to determine the SRR of HC1 and NH3 has larger uncertainties than that of SO2 and NOx, attention is needed to handle the difference.
Conclusion The damage function easily defines the concrete NPP damage due to an additional emission. The impact indica tor, NPP, also
has an advantage in its mass unit that is directly summable through the entire impact categories. Expansion of endpoints,
such as in aquatic ecosystems, material degradation, human health, and biodiversity aspects of terrestrial ecosystems, is
an important subject for future work. Further, uncertain analyses for major parameters will provide helpful information on
the reliability of damage function. 相似文献
79.
Murakami N Tamura S Koyama K Sugimoto M Maekawa R Kobayashi M 《Bioorganic & medicinal chemistry letters》2004,14(10):2597-2601
Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration different from 1. Additionally, conformation analysis among the two analogues and arenastatin A (1) indicated that the torsion angle from C-14 to C-20 is a conclusive factor for the potent cytotoxicity of 1. 相似文献
80.
Tanaka M Sagawa S Hoshi J Shimoma F Matsuda I Sakoda K Sasase T Shindo M Inaba T 《Bioorganic & medicinal chemistry letters》2004,14(20):5171-5174
We report herein synthesis of PKCbeta-selective inhibitors possessing the novel pharmacophore of anilino-monoindolylmaleimide. Several compounds of this series exhibited IC50's as low as 50 nM against human PKCbeta2. One of the most potent compounds, 6l, inhibited PKCbeta1 and PKCbeta2 with IC50 of 21 and 5 nM, respectively, and exhibited selectivity of more than 60-fold in favor of PKCbeta2 relative to other PKC isozymes (PKCalpha, PKCgamma, and PKCepsilon). 相似文献