全文获取类型
收费全文 | 1635篇 |
免费 | 87篇 |
国内免费 | 3篇 |
出版年
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 17篇 |
2018年 | 25篇 |
2017年 | 19篇 |
2016年 | 41篇 |
2015年 | 41篇 |
2014年 | 57篇 |
2013年 | 126篇 |
2012年 | 83篇 |
2011年 | 100篇 |
2010年 | 63篇 |
2009年 | 58篇 |
2008年 | 109篇 |
2007年 | 121篇 |
2006年 | 96篇 |
2005年 | 98篇 |
2004年 | 87篇 |
2003年 | 90篇 |
2002年 | 77篇 |
2001年 | 29篇 |
2000年 | 32篇 |
1999年 | 24篇 |
1998年 | 17篇 |
1997年 | 23篇 |
1996年 | 19篇 |
1995年 | 24篇 |
1994年 | 16篇 |
1993年 | 13篇 |
1992年 | 20篇 |
1991年 | 17篇 |
1990年 | 8篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 10篇 |
1984年 | 12篇 |
1983年 | 5篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 11篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有1725条查询结果,搜索用时 406 毫秒
981.
Nitta KR Takahashi S Haramoto Y Fukuda M Tanegashima K Onuma Y Asashima M 《The International journal of developmental biology》2007,51(4):321-325
Smad-interacting protein-1 (SIP1), also known as deltaEF2, ZEB2 and zfhx1b, is essential for the formation of the neural tube and the somites. Overexpression of Xenopus SIP1 causes ectopic neural induction via inhibition of bone morphogenetic protein (BMP) signaling and inhibition of Xbra expression. Here, we report the functional analyses of 4 domain-deletion mutants of XSIP1. Deletion of the N-terminus zinc finger domain suppressed neural induction and BMP inhibition, but these were not affected by deletion of the other domains (the Smad binding domain, the DNA-binding homeodomain together with the CtBP binding site and the C-terminus zinc finger). Therefore SIP1 does not inhibit BMP signaling by binding to Smad proteins. In contrast, all of the deletion constructs inhibited Xbra expression. These results suggest that the N-terminus zinc finger domain of XSIP1 has an important role in neural induction and that Xbra suppression occurs via a mechanism separate from the neural inducing activity. 相似文献
982.
983.
Aya Sugyo Atsushi B. Tsuji Hitomi Sudo Maki Okada Mitsuru Koizumi Hirokazu Satoh Gene Kurosawa Yoshikazu Kurosawa Tsuneo Saga 《PloS one》2015,10(4)
Objective
Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR), is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT) with 90Y-TSP-A01 in pancreatic cancer mouse models.Methods
TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2) was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02) were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.Results
MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.Conclusion
90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further investigation is necessary to improve the efficacy for the radioresistant types like BxPC-3. 相似文献984.
985.
Shimoda LA Luke T Sylvester JT Shih HW Jain A Swenson ER 《American journal of physiology. Lung cellular and molecular physiology》2007,292(4):L1002-L1012
Hypoxic pulmonary vasoconstriction (HPV) occurs with ascent to high altitude and can contribute to development of high altitude pulmonary edema (HAPE). Vascular smooth muscle contains carbonic anhydrase (CA), and acetazolamide (AZ), a CA inhibitor, blunts HPV and might be useful in the prevention of HAPE. The mechanism by which AZ impairs HPV is uncertain. Originally developed as a diuretic, AZ also has direct effects on systemic vascular smooth muscle, including modulation of pH and membrane potential; however, the effect of AZ on pulmonary arterial smooth muscle cells (PASMCs) is unknown. Since HPV requires Ca2+ influx into PASMCs and can be modulated by pH, we hypothesized that AZ alters hypoxia-induced changes in PASMC intracellular pH (pH(i)) or Ca2+ concentration ([Ca2+](i)). Using fluorescent microscopy, we tested the effect of AZ as well as two other potent CA inhibitors, benzolamide and ethoxzolamide, which exhibit low and high membrane permeability, respectively, on hypoxia-induced responses in PASMCs. Hypoxia caused a significant increase in [Ca2+](i) but no change in pH(i). All three CA inhibitors slightly decreased basal pH(i), but only AZ caused a concentration-dependent decrease in the [Ca2+](i) response to hypoxia. AZ had no effect on the KCl-induced increase in [Ca2+](i) or membrane potential. N-methyl-AZ, a synthesized compound lacking the unsubstituted sulfonamide group required for CA inhibition, had no effect on pH(i) but inhibited hypoxia-induced Ca2+ responses. These results suggest that AZ attenuates HPV by selectively inhibiting hypoxia-induced Ca2+ responses via a mechanism independent of CA inhibition, changes in pH(i), or membrane potential. 相似文献
986.
987.
Leila Hayashi Eurico C. Oliveira Genevieve Bleicher-Lhonneur Patrick Boulenguer Ricardo T. L. Pereira Roberto von Seckendorff Viviane T. Shimoda André Leflamand Patrick Vallée Alan T. Critchley 《Journal of applied phycology》2007,19(5):505-511
The yield and the quality of carrageenan depend, among other things, on the cultivar or strain and on the cultivation and
processing techniques. This work presents carrageenan yields and some properties of Kappaphycus alvarezii under selected cultivation conditions i.e. cultivation period, depth and planting density. Growth rates (GR) ranged from
5.2–7.2% day−1, with the highest GR at 28 days, at 0–0.5 m depth, and planting density of 12 and 8.4 plants m−2. Highest productivity was observed in samples after 44 and 59 day cultivation period, which were grown at 0–0.5 m depth,
and a planting density of 24 plants m−2. Carrageenan yields, iota fraction, viscosity, molecular weight and gel strength were measured. A cultivation period of 28 days during the winter had
a significant higher carrageenan yield, while samples from 59 days showed a significantly higher iota fraction. Carrageenan also presented an increasing molecular weight under longer cultivation periods. A similar trend was
observed for viscosity and gel strength. All samples cultivated in Brazil gave higher values when compared to a K. alvarezii commercial reference sample, with the exception of carrageenan yield values, which were lower in this study. Taking into
account all parameters, the culture condition which provided the best carrageenan from a commercial perspective were 45 days
of cultivation, growing at the surface, with a planting density of 12 plants m−2. Considering that this study was performed in the least favorable season (winter), these results indicate that the site is
suitable for the implementation of commercial cultivation. 相似文献
988.
The ability to form amyloid fibrils from a wide range of proteins would open up the opportunity to augment studies of the molecular basis of amyloid fibril formation. We investigated 36 different conditions with respect to four model proteins to evaluate their ability to form amyloid fibrils. In a 5% ethanol solution at pH 2 at 57 degrees C, hen egg white lysozyme, bovine beta-lactoglobulin, and bovine trypsinogen formed mature-type fibrils, while only histone H2A formed immature-type fibrils. Under these conditions, 25 of the 38 proteins formed amyloid fibrils. In addition, three additional proteins formed fibrils in a solution containing 5% trifluoroethanol instead of 5% ethanol. In summary, a total 28 proteins formed amyloid fibrils. Under these extreme conditions, chemical fragmentation was observed. Destabilization of the native structure, strengthening of hydrogen bonds, and chemical fragmentation are thought to play important roles in the formation of amyloid fibrils. 相似文献
989.
Akiko Takasuga Toshio Watanabe Yasushi Mizoguchi Takashi Hirano Naoya Ihara Atsushi Takano Kou Yokouchi Akira Fujikawa Kazuyoshi Chiba Naohiko Kobayashi Ken Tatsuda Toshiaki Oe Megumi Furukawa-Kuroiwa Atsuko Nishimura-Abe Tatsuo Fujita Kazuya Inoue Kazunori Mizoshita Atsushi Ogino Yoshikazu Sugimoto 《Mammalian genome》2007,18(2):125-136
To map quantitative trait loci (QTL) for growth and carcass traits in a purebred Japanese Black cattle population, we conducted
multiple QTL analyses using 15 paternal half-sib families comprising 7860 offspring. We identified 40 QTL with significant
linkages at false discovery rates of less than 0.1, which included 12 for intramuscular fat deposition called marbling and
12 for cold carcass weight or body weight. The QTL each explained 2%–13% of the phenotypic variance. These QTL included many
replications and shared hypothetical identical-by-descent (IBD) alleles. The QTL for CW on BTA14 was replicated in five families
with significant linkages and in two families with a 1% chromosome-wise significance level. The seven sires shared a 1.1-Mb
superior Q haplotype as a hypothetical IBD allele that corresponds to the critical region previously refined by linkage disequilibrium
mapping. The QTL for marbling on BTA4 was replicated in two families with significant linkages. The QTL for marbling on BTA6,
7, 9, 10, 20, and 21 and the QTL for body weight on BTA6 were replicated with 1% and/or 5% chromosome-wise significance levels.
There were shared IBD Q or q haplotypes in the marbling QTL on BTA4, 6, and 10. The allele substitution effect of these haplotypes ranged from 0.7 to
1.2, and an additive effect between the marbling QTL on BTA6 and 10 was observed in the family examined. The abundant and
replicated QTL information will enhance the opportunities for positional cloning of causative genes for the quantitative traits
and efficient breeding using marker-assisted selection.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users. 相似文献
990.
The yeast prion [PSI(+)] represents an aggregated state of the translation termination factor Sup35 resulting in the tendency of ribosomes to readthrough stop codons. In this study, we constructed an auxotrophic chromosomal marker, ura3-197 (nonsense allele), applicable to selection for loss of [PSI(+)] to [psi(-)]. Unlike [psi(-)] yeast strains, [PSI(+)] yeast strains exhibit nonsense suppression of the ura3-197 allele and are not viable in the presence of 5-fluoroorotic acid (5-FOA) that is converted to a toxic material by the readthrough product of Ura3. We selected 20 5-FOA-resistant, loss-of-[PSI(+)], mutants spontaneously or by transposon-mediated mutagenesis from ura3-197[PSI(+)] cells. All of the 20 [psi(-)] isolates were affected in Hsp104, a protein-remodelling factor. Although most of them were disabled in a normal Hsp104 function for thermotolerance, three single mutants, L462R, P557L and D704N, remained thermotolerant. Importantly, L462R and D704N also eliminate other yeast prions [URE3] and [PIN(+)], while P557L does not, suggesting that Hsp104 harbours a unique activity to prion propagation independent of its function in thermotolerance. The mutations that are specific to prion propagation are clustered around the lateral channel of the Hsp104 hexamer, suggesting a crucial and specific role of this channel for prion propagation. 相似文献