全文获取类型
收费全文 | 1077篇 |
免费 | 79篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 15篇 |
2017年 | 20篇 |
2016年 | 34篇 |
2015年 | 49篇 |
2014年 | 44篇 |
2013年 | 62篇 |
2012年 | 69篇 |
2011年 | 63篇 |
2010年 | 53篇 |
2009年 | 30篇 |
2008年 | 60篇 |
2007年 | 69篇 |
2006年 | 66篇 |
2005年 | 44篇 |
2004年 | 56篇 |
2003年 | 51篇 |
2002年 | 46篇 |
2001年 | 20篇 |
2000年 | 30篇 |
1999年 | 16篇 |
1998年 | 6篇 |
1997年 | 13篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 16篇 |
1990年 | 4篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1973年 | 7篇 |
排序方式: 共有1156条查询结果,搜索用时 15 毫秒
61.
62.
Rachna Aneja Antonella Grigoletto Aakansha Nangarlia Adel A. Rashad Steven Wrenn Jeffrey M. Jacobson Gianfranco Pasut Irwin Chaiken 《Journal of peptide science》2019,25(4)
Previously, we reported the discovery of macrocyclic peptide triazoles (cPTs) that bind to HIV‐1 Env gp120, inhibit virus cell infection with nanomolar potencies, and cause irreversible virion inactivation. Given the appealing virus‐killing activity of cPTs and resistance to protease cleavage observed in vitro, we here investigated in vivo pharmacokinetics of the cPT AAR029b. AAR029b was investigated both alone and encapsulated in a PEGylated liposome formulation that was designed to slowly release inhibitor. Pharmacokinetic analysis in rats showed that the half‐life of FITC‐AAR029b was substantial both alone and liposome‐encapsulated, 2.92 and 8.87 hours, respectively. Importantly, liposome‐encapsulated FITC‐AAR029b exhibited a 15‐fold reduced clearance rate from serum compared with the free FITC‐cPT. This work thus demonstrated both the in vivo stability of cPT alone and the extent of pharmacokinetic enhancement via liposome encapsulation. The results obtained open the way to further develop cPTs as long‐acting HIV‐1 inactivators against HIV‐1 infection. 相似文献
63.
64.
A dense single-nucleotide polymorphism-based genetic linkage map of grapevine (Vitis vinifera L.) anchoring Pinot Noir bacterial artificial chromosome contigs 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Troggio M Malacarne G Coppola G Segala C Cartwright DA Pindo M Stefanini M Mank R Moroldo M Morgante M Grando MS Velasco R 《Genetics》2007,176(4):2637-2650
The construction of a dense genetic map for Vitis vinifera and its anchoring to a BAC-based physical map is described: it includes 994 loci mapped onto 19 linkage groups, corresponding to the basic chromosome number of Vitis. Spanning 1245 cM with an average distance of 1.3 cM between adjacent markers, the map was generated from the segregation of 483 single-nucleotide polymorphism (SNP)-based genetic markers, 132 simple sequence repeats (SSRs), and 379 AFLP markers in a mapping population of 94 F(1) individuals derived from a V. vinifera cross of the cultivars Syrah and Pinot Noir. Of these markers, 623 were anchored to 367 contigs that are included in a physical map produced from the same clone of Pinot Noir and covering 352 Mbp. On the basis of contigs containing two or more genetically mapped markers, region-dependent estimations of physical and recombinational distances are presented. The markers used in this study include 118 SSRs common to an integrated map derived from five segregating populations of V. vinifera. The positions of these SSR markers in the two maps are conserved across all Vitis linkage groups. The addition of SNP-based markers introduces polymorphisms that are easy to database, are useful for evolutionary studies, and significantly increase the density of the map. The map provides the most comprehensive view of the Vitis genome reported to date and will be relevant for future studies on structural and functional genomics and genetic improvement. 相似文献
65.
Rho GJ Coppola G Sosnowski J Kasimanickam R Johnson WH Semple E Mastromonaco GF Betts DH Koch TG Weese S Hewson J Hayes MA Kenney DG Basrur PK King WA 《Cloning and stem cells》2007,9(1):118-129
Animal models have played an important part in establishing our knowledge base on reproduction, development, and the occurrence and impact of chromosome abnormalities. Translocations involving the X chromosome and an autosome are unique in that they elicit sex-dependent infertility, with male carriers rendered sterile by synaptic anomalies during meiosis, whereas female carriers conceive but repeatedly abort. Until now the limited access to relevant fetal oocytes has precluded direct study of meiotic events in female carriers. Because somatic cell nuclear transfer (SCNT) circumvents meiotic problems associated with fertility disturbances in translocation carriers, we used SCNT to generate embryos, fetuses, and calves from a cell line derived from a deceased subfertile X-autosome translocation carrier cow to study the meiotic configurations in carrier oocytes. Data from 33 replicates involving 2470 oocyte-donor-cell complexes were assessed for blastocyst development and of these, 42 blastocysts were transferred to 21 recipients. Fourteen pregnancies were detected on day 35 of gestation. One of these was sacrificed for ovary retrieval on day 94 and three went to term. Features of oocytes from the fetal ovary and from the newborn ovaries were examined. Of the pachytene spreads analyzed, 16%, 82%, and 1.5% exhibited quadrivalent, trivalent/univalent, and bivalent/univalent/univalent structures, respectively, whereas among the diakinesis/metaphase I spreads, 16% ring, 75% chain, and 8.3% bivalent/bivalent configurations were noted, suggesting that the low fertility among female carriers may be related to synaptic errors in a predominant proportion of oocytes. Our results indicate that fibroblasts carrying the X-autosome translocation can be used for SCNT to produce embryos, fetuses, and newborn clones to study such basic aspects of development as meiosis and to generate carriers that cannot easily be reproduced by conventional breeding. 相似文献
66.
Marco Savioli Lorenzo Antonelli Gianfranco Bocchinfuso Francesca Cavalieri Rita Cimino Emanuela Gatto Ernesto Placidi Julio Raul Fernandez Masso Hilda Garay Perez Hector Santana Maribel Guerra-Vallespi Mariano Venanzi 《Journal of peptide science》2022,28(1):e3356
Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution. 相似文献
67.
Sharan SK Pyle A Coppola V Babus J Swaminathan S Benedict J Swing D Martin BK Tessarollo L Evans JP Flaws JA Handel MA 《Development (Cambridge, England)》2004,131(1):131-142
The role of Brca2 in gametogenesis has been obscure because of embryonic lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC with the BRCA2 gene. This construct rescues embryonic lethality and the mice develop normally. However, there is poor expression of the transgene in the gonads and the mice are infertile, allowing examination of the function of BRCA2 in gametogenesis. BRCA2-deficient spermatocytes fail to progress beyond the early prophase I stage of meiosis. Observations on localization of recombination-related and spermatogenic-related proteins suggest that the spermatocytes undergo early steps of recombination (DNA double strand break formation), but fail to complete recombination or initiate spermiogenic development. In contrast to the early meiotic prophase arrest of spermatocytes, some mutant oocytes can progress through meiotic prophase I, albeit with a high frequency of nuclear abnormalities, and can be fertilized and produce embryos. Nonetheless, there is marked depletion of germ cells in adult females. These studies provide evidence for key roles of the BRCA2 protein in mammalian gametogenesis and meiotic success. 相似文献
68.
Tavío MM Perilli M Vila J Becerro P Casañas L Amicosante G Jiménez de Anta MT 《FEMS microbiology letters》2004,238(1):139-144
The effect of salicylate, a marRAB inducer, on the resistance to beta-lactams was characterized in an AmpC beta-lactamase hyperproducer Morganella morganii clinical isolate (the M1 strain). Results were compared with those of the effect of salicylate in a wild-type M. morganii strain. Salicylate induced a decreased susceptibility to nalidixic acid, norfloxacin and tetracycline and simultaneously increased the susceptibility to beta-lactams apparently due to the repression of AmpC beta-lactamase synthesis in the M1 strain. Likewise, salicylate only repressed 46 kDa outer membrane protein expression in the wild-type strain, since the clinical isolate M1 did not express it. 相似文献
69.
Drago M Chessa M Gianfranco B Bossone E Carminati M 《International journal of cardiovascular interventions》2004,6(3-4):156-159
We describe a case of a congenital coronary artery fistula of the right coronary artery draining into the left atrium in an eight-year-old boy. The initial diagnosis was made after the detection of a continuous cardiac murmur at the age of six years. Transthoracic echocardiography showed the right coronaric ostium dilatation, the site of drainage in the left atrium and left ventricle volume overload. Catheterization confirmed the diagnosis. The patient underwent percutaneous closure by PDA occluder device. Immediate post-closure angiograms showed complete occlusion of the fistula. The patient showed transient ischemic changes on ECG associated to an increase of plasmatic levels of the cardiac enzyme. ECG and cardiac enzyme were normal one week after the procedure. 相似文献
70.
The PN(2)S N-(N-(3-diphenylphosphinopropionyl)glycyl)cysteine ligand was conjugated to methoxy-poly(ethylene glycol)-amino (mPEG-NH(2)) 5 and 20 kDa to yield PN(2)S(Trt)-PEG(5000) 1 and PN(2)S(Trt)-PEG(20000) 2, and then detritylated to PN(2)S-PEG(5000) 4 and PN(2)S-PEG(20000) 5. When an acidic solution of (99m)TcO(4)(-) is added to 4 or 5 in solid form, a quantitative yield in a single labeled species, (99m)Tc-labeled PN(2)S-PEG(5000) 9 and (99m)Tc-labeled PN(2)S-PEG(20000) 10, respectively, is obtained. The reaction occurs in less than 15 min at room temperature for 4 and 35 degrees C for 5. This labeling procedure avoids the use of an external reducing agent, and it is based on the amphiphilic properties of PN(2)S-PEGs. Once in water, 4 and 5 self-assemble in micelles, which catalyze the metal reduction by means of an electron pair transfer from the phosphorus to technetium. The [(99m)TcO](3+) species is then coordinated, and at micelle level, both the (P)ON(2)S and the PN(2)S coordinations are possible, as demonstrated by reacting (99m)Tc-gluconate and ReOCl(3)(PPh(3))(2) with 4 and 5 and with the oxidized analogous (P)ON(2)S-PEG(5000) 6. Compounds 9 and 10 exhibited a high stability both in vitro and in vivo. Biodistribution studies in mice also indicated that PN(2)S linking and (99m)Tc labeling do not modify PEG behavior in water and in vivo since the polymer dictates the fate of the conjugate. 相似文献