全文获取类型
收费全文 | 854篇 |
免费 | 42篇 |
国内免费 | 26篇 |
专业分类
922篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 18篇 |
2021年 | 19篇 |
2020年 | 19篇 |
2019年 | 32篇 |
2018年 | 19篇 |
2017年 | 14篇 |
2016年 | 16篇 |
2015年 | 19篇 |
2014年 | 29篇 |
2013年 | 48篇 |
2012年 | 21篇 |
2011年 | 31篇 |
2010年 | 35篇 |
2009年 | 33篇 |
2008年 | 42篇 |
2007年 | 37篇 |
2006年 | 39篇 |
2005年 | 43篇 |
2004年 | 47篇 |
2003年 | 38篇 |
2002年 | 32篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 18篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 22篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 14篇 |
1989年 | 13篇 |
1988年 | 7篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1982年 | 11篇 |
1981年 | 7篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有922条查询结果,搜索用时 0 毫秒
151.
《Nucleosides, nucleotides & nucleic acids》2013,32(4):247-257
Synthesis and stereochemical characterization of enantiomerically pure nucleoside-3′-phosphorothioate esters and salts are reported. Vicinal carbon–phosphorus couplings reflect different predominance of the ? conformation in the isomeric (Rp and Sp) esters, while for the salts the ?t conformation prevails in both stereoisomers. The influence of solvent and temperature on the conformational preferences is also described. 相似文献
152.
P34, a storage protein and major soybean allergen, has undergone a functional transition from a cysteine peptidase to a syringolide receptor. An exploration of the evolutionary mechanism of this functional transition is made. To identify homologous genes of P34, syntenic network was constructed using syntenic relationships from the Plant Genome Duplication Database. The collected homologous genes, along with SPE31, a highly homologous protein to P34 from the seeds of Pachyrhizus erosus, were used to construct a phylogenetic tree. The results show that multiple gene duplications, exon shuffling and following granulin domain loss and some critical point mutations are associated with the functional transition. Although some tests suggested the existence of positive selection, the possibility that random fixation under relaxation of purifying selection results in the functional transition is also supported. In addition, the genes Glyma08g12340 and Medtr8g086470 may belong to a new group within the papain family. 相似文献
153.
Josef Matoušek 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2001,129(3):175-191
The antitumor effect of ribonucleases was studied with animal ribonucleolytic enzymes, bovine pancreatic RNase A, bovine seminal RNase (BS-RNase), onconase and angiogenin. While bovine pancreatic RNase A exerts a minor antitumor effect, BS-RNase and onconase exert significant effects. Angiogenin, as RNase, works in an opposite way, it initiates vascularization of tumors and subsequent tumor growth. Ribonunclease inhibitors are not able to inhibit the antitumor effectiveness of BS-RNase or onconase. However, they do so in the case of pancreatic RNases. Conjugation of BS-RNase with antibodies against tumor antigens (preparation of immunotoxins) like the conjugation of the enzyme with polymers enhances the antitumor activity of the ribonuclease. After conjugation with polymers, the half-life of BS-RNase in blood is extended and its immunogenicity reduced. Recombinant RNases have the same functional activity as the native enzymes. The synthetic genes have also been modified, some of them with gene sequences typical for the BS-RNase parts. Recent experimental efforts are directed to the preparation of ‘humanized antitumor ribonuclease’ that would be structurally similar to human enzyme with minimal immunogenicity and side effects. The angiogenesis of tumors is attempted to be minimized by specific antibodies or anti-angiogenic substances. 相似文献
154.
FBXL20 promotes breast cancer malignancy by inhibiting apoptosis through degradation of PUMA and BAX
Rajesh Kumar Manne Yashika Agrawal Sunil K. Malonia Shahid Banday Sarathkumar Edachery Asha Patel Avinash Kumar Praveenkumar Shetty Manas Kumar Santra 《The Journal of biological chemistry》2021,297(4)
Apoptosis is a programmed cell death that efficiently removes damaged cells to maintain tissue homeostasis. Defect in apoptotic machinery can lead to tumor development, progression, and resistance to chemotherapy. PUMA (p53 upregulated modulator of apoptosis) and BAX (BCL2-associated X protein) are among the most well-known inducers of apoptosis. It has been reported that expression levels of BAX and PUMA are controlled at the posttranslational level by phosphorylation. However, the posttranslational regulation of these proapoptotic proteins remains largely unexplored. In this study, using biochemical, molecular biology, flow cytometric, and immunohistochemistry techniques, we show that PUMA and BAX are the direct target of the F-box protein FBXL20, which restricts their cellular levels. FBXL20 directs the proteasomal degradation of PUMA and BAX in a protein kinase AKT1-dependent manner to promote cancer cell proliferation and tumor growth. Interestingly, inactivation of AKT1 results in activation of another protein kinase GSK3α/β, which facilitates the proteasomal degradation of FBXL20 by another F-box protein, FBXO31. Thus, a switch between two signaling kinases AKT1 and GSK3α/β modulates the functional activity of these proapoptotic regulators, thereby determining cell survival or death. RNAi-mediated ablation of FBXL20 results in increased levels of PUMA as well as BAX, which further enhances the sensitivity of cancer cells to chemotherapeutic drugs. We showed that high level expression of FBXL20 in cancer cells reduces therapeutic drug-induced apoptosis and promotes chemoresistance. Overall, this study highlights the importance of targeting FBXL20 in cancers in conjunction with chemotherapy and may represent a promising anticancer strategy to overcome chemoresistance. 相似文献
155.
Toshihiko Kimura Masataka Watanabe Kunio Kohata Ryuichi Sudo 《Journal of applied phycology》1999,11(3):301-311
The ecological advantage of diel vertical migration on the nutrition and accumulation of Chattonella antiqua, which is one
of the dominant red-tide forming phytoplankton species in the Seto Inland Sea of Japan, was examined using a large axenic
culture tank, in which vertical stratification of salinity, temperature and nutrients was maintained, analogous to natural
conditions observed when red tides occur. C. antiqua was capable of migrating through very sharp salinity and temperature
gradients. At night the species migrated to the deep nutrient-rich water and assimilated nutrients. During the daytime it
migrated to the nutrient-depleted surface water and used the accumulated nutrients for photosynthesis. Nitrogen uptake was
synchronized with phosphate uptake. 31P-NMR spectroscopy during the migration experiment revealed that C. antiqua has the capability of nocturnal phosphate uptake
in the deep nutrient-rich water, but no capability of synthesizing polyphosphate, which was considered to be the intracellular
phosphate pool. These findings were compared with those reported for another raphidophycean, Heterosigma akashiwo. Although
both species carry out vertical migration and nocturnal nutrient uptake, only H. akashiwo has the capability of making an
intracellular polyphosphate pool.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
156.
Nikolai N. Khodarev Irina A. Sokolova Andrew T.M. Vaughan 《Journal of cellular biochemistry》1998,70(4):604-615
We have addressed the association between the site of DNA cleavage during apoptosis and DNA replication. DNA double strand breaks were introduced into chromatin containing pulse labeled nascent DNA by the induction of apoptosis or autocleavage of isolated nuclei. The location of these breaks in relation to nascent DNA were revealed by Bal 31 exonuclease digestion at the cut sites. Our data show that Bal31 accessible cut sites are directly linked to regions enriched in nascent DNA. We suggest that these regions coincide with the termini of replication domains, possibly linked by strong DNA-matrix interactions with biophysically defined topological structures of 0.5 - 1.3 Mbp in size. The 50 kbp fragments that are commonly observed as products of apoptosis are also enriched in nascent DNA within internal regions but not at their termini. It is proposed that these fragments contain a subset of replicon DNA that is excised during apoptosis through recognition of their weak attachment to the nuclear matrix within the replication domain.J. Cell. Biochem. 70:604-615, 1998. © 1998 Wiley-Liss, Inc. © 1998 Wiley-Liss, Inc. 相似文献
157.
Packiarajan M Marzabadi MR Desai M Lu Y Noble SA Wong WC Jubian V Chandrasena G Wolinsky TD Zhong H Walker MW Wiborg O Andersen K 《Bioorganic & medicinal chemistry letters》2011,21(18):5436-5441
The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6-dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress. 相似文献
158.
The subcellular site of -amylase (EC 1.6.2.1) synthesis and transport was studied in barley aleurone layers incubated in the presence or absence of gibberellic acid (GA3). Using [35S]methionine as a marker, the site of amino-acid incorporation into organelles isolated from aleurone layers incubated with and without GA3 was determined following purification by isopycnic sucrose-density-gradient centrifugation. Incorporation of radioactivity into trichloroacetic-acid-insoluble proteins was greatest in those fractions exhibiting activity of an endoplasmic reticulum (ER) marker enzyme. Further fractionation of densitygradient fractions by sodium-dodecyl-sulfate polyacrylamide-gel electrophoresis showed that a major portion of the radioactivity in the ER fractions was present in a protein co-migrating with marker -amylase. This protein was identified as authentic -amylase by immunoadsorbent chromatography and affinity chromatography. The newly synthesized -amylase associated with the ER was shown to be sequenstered within the lumen of the ER by experiments which showed that the enzyme was resistant to proteolytic degradation. The labelled -amylase sequestered in the ER can be chased from this organelle when tissue is incubated in unlabelled methionine following a 1-h pulse of labelled methionine. The isoenzymic forms of -amylase found in tissue homogenates and incubation media of aleurone layers incubated with and without GA3 were characterized after chromatography on diethylaminoethyl cellulose. In homogenates of GA3-treated aleurone layers, five peaks of -amylase activity were detected, while in homogenates of aleurone layers incubated with-out GA3 only three peaks of activity were found. In incubation media, four isoenzymes were found after GA3 treatment and two were found after incubation without GA3. We conclude that at least five -amylase isoenzymes are synthesized by the ER of barley aleurone layers and that this membrane system is involved in the sequestration and transport of four of these isoenzymes.Abbreviations CHA
cyclohepataamylose
- DEAE-cellulose
diethylaminoethyl-cellulose
- ER
endoplasmic reticulum
- GA3
gibberellic acid
- SDS-PAGE
sodium-dodecyl-sulfate polyacrylamide-gel electrophoresis 相似文献
159.
目的:探索孟鲁司特钠联合布地奈德混悬液对哮喘急性发作患儿血清嗜酸性粒细胞(EOS)、嗜酸性粒细胞阳离子蛋白(ECP)水平和肺功能的影响。方法:选择自2015年10月至2016年10月我院收治的200例支气管哮喘急性发作患儿,按照随机数表法分成观察组和对照组各100例。对照组患儿口服孟鲁司特钠,观察组患儿在对照组基础上给予布地奈德气雾剂进行雾化治疗,两组均治疗1周。统计分析两组患儿的临床有效率,肺功能指标,包括第1秒用力呼气容积(FEV1)、用力肺活量(FVC)及FEV1/FVC,对比治疗前后两组患儿血清中EOS、ECP水平的变化。结果:治疗后,观察组的总有效率为97.00%,显著高于对照组的81.00%(P0.05);经治疗后两组患儿肺功能指标均较治疗前明显改善,且观察组患儿优于对照组(P0.05);两组患儿治疗后EOS、ECP水平均低于治疗前,而观察组患儿低于对照组,差异均有统计学意义(P0.05)。结论:孟鲁司特钠联合布地奈德对于小儿哮喘的急性发作具有良好的临床疗效,能显著改善患儿肺功能和血清中炎症因子的水平,减轻患儿体内的炎症反应,值得在临床上推广应用。 相似文献
160.
Changes in high-energy phosphate metabolites and the intracellular pH (pHi) were monitored in cerebral tissue during periods of hypoglycaemia and hypoxia using 31P nuclear magnetic resonance spectroscopy. Superfused brain slices were loaded with deoxyglucose at a concentration shown not to impair cerebral metabolism, and the chemical shift of the resulting 2-deoxyglucose-6-phosphate (DOG6P) peak was used to monitor the pHi. In some experiments with low circulating levels of Pi, the intracellular Pi was visible and indicated a pH identical to that of DOG6P, an observation validating its use as an indicator of pHi in cerebral tissue. The pHi was found to be unchanged during moderate hypoglycaemia; however, mild hypoxia (PO2 = 16.4 kPa) and severe hypoglycaemia produced marked reductions from the normal of 7.2 to 6.8 and 7.0, respectively. Hypoglycaemia caused a fall in the level of both phosphocreatine (PCr) and ATP, whereas hypoxia affected PCr alone, as shown previously. However, the fall in pHi was similar during the two insults, thus indicating that the change in pH is not directly linked to lactate production or to the creatine kinase reaction. 相似文献