全文获取类型
收费全文 | 2789篇 |
免费 | 153篇 |
国内免费 | 1篇 |
专业分类
2943篇 |
出版年
2022年 | 14篇 |
2021年 | 34篇 |
2020年 | 21篇 |
2019年 | 23篇 |
2018年 | 35篇 |
2017年 | 30篇 |
2016年 | 52篇 |
2015年 | 84篇 |
2014年 | 102篇 |
2013年 | 131篇 |
2012年 | 190篇 |
2011年 | 147篇 |
2010年 | 113篇 |
2009年 | 120篇 |
2008年 | 155篇 |
2007年 | 153篇 |
2006年 | 148篇 |
2005年 | 155篇 |
2004年 | 159篇 |
2003年 | 166篇 |
2002年 | 143篇 |
2001年 | 51篇 |
2000年 | 52篇 |
1999年 | 44篇 |
1998年 | 59篇 |
1997年 | 28篇 |
1996年 | 32篇 |
1995年 | 30篇 |
1994年 | 30篇 |
1993年 | 32篇 |
1992年 | 30篇 |
1991年 | 31篇 |
1990年 | 19篇 |
1989年 | 28篇 |
1988年 | 20篇 |
1987年 | 11篇 |
1986年 | 20篇 |
1985年 | 20篇 |
1984年 | 23篇 |
1983年 | 23篇 |
1982年 | 20篇 |
1981年 | 23篇 |
1980年 | 17篇 |
1979年 | 18篇 |
1978年 | 15篇 |
1977年 | 11篇 |
1976年 | 13篇 |
1975年 | 14篇 |
1974年 | 13篇 |
1966年 | 10篇 |
排序方式: 共有2943条查询结果,搜索用时 0 毫秒
121.
J A Marino A H Davis P J Spagnuolo 《Biochemical and biophysical research communications》1987,146(3):1132-1138
To investigate whether peripheral blood granulocytes can synthesize the adhesive glycoprotein, fibronectin, we sought to demonstrate the presence of messenger RNA coding for fibronectin within mature circulating granulocytes. Polyadenylated-enriched RNA was isolated from human peripheral blood granulocytes, human skin fibroblasts (synthesize fibronectin) and HeLa cells (lack fibronectin) and probed with a cDNA clone coding for the cell attachment domain of fibronectin. Hybridization of a fibronectin cDNA fragment occurred with fibroblast RNA but did not occur with granulocyte RNA despite a 100 fold excess granulocyte RNA. Incubation of granulocytes with n-formyl methionyl leucyl phenylalanine, a chemotactic peptide known to augment the release of fibronectin from granulocytes, failed to induce detectable levels of mRNA for fibronectin in granulocytes. There was no difference in the quantity of fibronectin released from chemotactic peptide-stimulated granulocytes pre-incubated in the presence or absence of the protein synthesis inhibitor, cycloheximide, suggesting that fibronectin exists in a stored form in granulocytes. These data suggest that fibronectin in mature granulocytes is the product of synthesis during early myeloid maturation. 相似文献
122.
Véronique Marie Patrice Gonzalez Magalie Baudrimont Jean-Paul Bourdineaud Alain Boudou 《Biometals》2006,19(4):399-407
Metallothionein (MT) response to cadmium (Cd) and zinc (Zn) bioaccumulation after single or combined direct exposure was compared
in two freshwater bivalves, Dreissena polymorpha (zebra mussel) and Corbicula fluminea (Asiatic clam). Bivalves were exposed to 0.133 μM Cd and/or 15.3 μM Zn, with metal and MT concentrations analysed in the
whole soft body after 1, 3, 10 and 24 days of exposure and compared with controls. Results showed significant increase in
MT concentrations in both species exposed to Cd and Cd+Zn with a higher accumulation of the protein compared to the control
in D. polymorpha for nevertheless similar Cd levels accumulated with time. Exposure to Zn alone led to a significant increase in MT concentrations
only in C. fluminea, whereas there was a lack of MT gene induction in the zebra mussels which was confirmed by MT mRNA quantification in gills
(RT-PCR). Mussel mortality after 10 days of exposure to Zn and Cd + Zn is discussed with regard to detoxification mechanisms,
which include metallothioneins. 相似文献
123.
A Marino E Salgado M Trueba J M Macarulla 《Comparative biochemistry and physiology. B, Comparative biochemistry》1986,85(4):795-803
The synthesis of phosphatidylcholine from phosphatidylethanolamine is carried out by chick liver microsomes (Gallus domesticus). Different concentrations of PE, NPE and NNPE were used as exogenous substrates. Saturation of the S-adenosylmethionine has been found for the three different reactions with or without exogenous substrate. Kinetic parameters have been determined for this enzyme system in chick liver microsomes. The three methyl reactions had a similar pH profile with an optimum at pH = 8. Divalent ions such as Ca2+ or Mg2+ did not stimulate the enzyme activity. The results suggest that the synthesis of phosphatidylcholine from phosphatidylethanolamine by chick liver microsomes exhibits a kinetic pattern with different aspects than that described for other animal or human preparations. 相似文献
124.
Bosselut N Van Ghelder C Claverie M Voisin R Onesto JP Rosso MN Esmenjaud D 《Plant cell reports》2011,30(7):1313-1326
Resistant rootstocks offer an alternative to pesticides for the control of soil pests. In Prunus spp., resistance loci to root-knot nematodes (RKN) have been mapped and a transformation method is needed to validate candidate genes. Our efforts have focused on the generation of transformed hairy-roots and composite plants appropriate for nematode infection assays. An efficient and reliable method using the A4R strain of Agrobacterium rhizogenes for the transformation of Prunus roots with an Egfp reporter gene is given. The rooting efficiency, depending on the genotypes, was maximal for the interspecific hybrid 253 (Myrobalan plum?×?almond-peach), susceptible to RKN, that was retained for subsequent studies. From the agro-inoculated cuttings, 72% produced roots, mainly at the basal section of the stem. Transformed roots were screened by microscope detection of Egfp fluorescence and molecular analyses of the integration of the transgene. The absence of residual agrobacteria in the plants was checked by the non-amplification of the chromosomal gene chvH. Egfp was expressed visually in 76% of the rooted plants. Isolated hairy roots in Petri dishes and composite plants (transformed roots and non-transformed aerial part) in soil containers were inoculated with the RKN Meloidogyne incognita. In both cases, root transformation did not affect the ability of the nematodes to develop in the root tissues. Our results showed that isolated hairy-roots can be used to validate candidate genes and the conditions in which composite plants offer a complementary system for studying the function of root genes in physiological conditions of whole plants are discussed. 相似文献
125.
Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy. 相似文献
126.
Two simple procedures for the synthesis of 2-deoxy-D-lyxo-hexono-1,4-lactone are described. Reductive cleavage of a 2-O-tosyl derivative of D-galactono-1,4-lactone in the presence of sodium iodide afforded the 2-deoxy derivative. On the other hand, alpha-deoxygenation of D-galactono-1,4-lactone was easily achieved by photochemical electron transfer deoxygenation of HO-2 as the 3-(trifluoromethyl)benzoate. Methyl 2-deoxy-beta-D-lyxo-hexafuranoside ('methyl 2-deoxy-beta-D-galactofuranoside') was synthesized and tested as substrate for exo beta-D-galactofuranosidase from Penicillium fellutanum. The reaction was followed by HPAEC, showing that methyl 2-deoxy-beta-D-galactofuranoside was not hydrolyzed by incubation with the enzyme. Neither the 2-deoxy lactone, nor the 2-deoxy-beta-D-galactofuranoside acted as inhibitors of the reaction with the 4-nitrophenyl beta-D-galactofuranoside. The present and our previous results show that the hydroxyl groups at C-2, C-3 and C-6 of the galactofuranoside are essential for interaction with the exo beta-D-galactofuranosidase. 相似文献
127.
Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single-knockout mice 下载免费PDF全文
Kuprash DV Alimzhanov MB Tumanov AV Grivennikov SI Shakhov AN Drutskaya LN Marino MW Turetskaya RL Anderson AO Rajewsky K Pfeffer K Nedospasov SA 《Molecular and cellular biology》2002,22(24):8626-8634
Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation, costimulation, inhibition, or cell death, depending on the type and status of the target cell. TNF, lymphotoxin alpha (LTalpha), and LTbeta form a subfamily of a larger family of TNF-related ligands with their genes being linked within a compact 12-kb cluster inside the major histocompatibility complex locus. Singly TNF-, LTalpha-, and LTbeta-deficient mice share several phenotypic features, suggesting that TNF/LT signaling pathways may regulate overlapping sets of target genes. In order to directly address the issue of redundancy of TNF/LT signaling, we used the Cre-loxP recombination system to create mice with a deletion of the entire TNF/LT locus. Mice with a triple LTbeta/TNF/LTalpha deficiency essentially manifest a combination of LT and TNF single-knockout phenotypes, except for microarchitecture of the spleen, where the disorder of lymphoid cell positioning and functional T- and B-cell compartmentalization is severer than that found in TNF or LT single-knockout mice. Thus, our data support the notion that TNF and LT have largely nonredundant functions in vivo. 相似文献
128.
Kim J. M. Mulders Yannick Weesepoel Packo P. Lamers Jean-Paul Vincken Dirk E. Martens René H. Wijffels 《Journal of applied phycology》2013,25(5):1421-1430
The effect of three different nutrient depletions (nitrogen, sulphur and magnesium) on the growth and pigment accumulation of the haptophyte Isochrysis aff. galbana (clone T-ISO) has been studied. Pigments were quantified based on RP-UHPLC-PDA-MSn analysis. All nutrient depletions led to reduced maximal biomass concentrations. Besides, all nutrient-depleted cultures accumulated 3-hydroxyechinenone. To our knowledge, this is the first time that 3-hydroxyechinenone has been found in I. aff. galbana T-ISO. Most 3-hydroxyechinenone, as well as the most echinenone and diatoxanthin, were found in the nitrogen-limited culture in which a more severe limitation resulted in higher cellular contents. Similar to accumulation of diatoxanthin, accumulation of 3-hydroxyechinenone and echinenone may be part of a global (stress) response mechanism to oversaturating light conditions. 相似文献
129.
Jeronymo Dalapicolla Ronnie Alves Rodolfo Jaff Santelmo Vasconcelos Eder Soares Pires Gisele Lopes Nunes Jovani Bernardino de Souza Pereira Jos Tasso F. Guimares Mariana C. Dias Taís Nogueira Fernandes Daniela Scherer Fernando Marino Gomes dos Santos Alexandre Castilho Mirella Pupo Santos Emiliano Nicolas Caldern Rodrigo Lemes Martins Rodrigo Nunes da Fonseca Francisco de Assis Esteves Cecílio Frois Caldeira Guilherme Oliveira 《Ecology and evolution》2021,11(15):10119
The quillwort Isoëtes cangae is a critically endangered species occurring in a single lake in Serra dos Carajás, Eastern Amazon. Low genetic diversity and small effective population sizes (N e) are expected for narrow endemic species (NES). Conservation biology studies centered in a single species show some limitations, but they are still useful considering the limited time and resources available for protection of species at risk of extinction. Here, we evaluated the genetic diversity, population structure, N e, and minimum viable population (MVP) of I. cangae to provide information for effective conservation programs. Our analyses were based on 55 individuals collected from the Amendoim Lake and 35,638 neutral SNPs. Our results indicated a single panmictic population, moderate levels of genetic diversity, and N e in the order of thousands, contrasting the expected for NES. Negative FIS values were also found, suggesting that I. cangae is not under risk of inbreeding depression. Our findings imply that I. cangae contains enough genetic diversity to ensure evolutionary potential and that all individuals should be treated as one demographic unit. These results provide essential information to optimize ex situ conservation efforts and genetic diversity monitoring, which are currently applied to guide I. cangae conservation plans. 相似文献
130.
Camille V. Chagneau Clmence Massip Nadge Bossuet-Greif Christophe Fremez Jean-Paul Motta Ayaka Shima Cline Besson Pauline Le Faouder Nicolas Cnac Marie-Paule Roth Hlne Coppin Maxime Fontani Patricia Martin Jean-Philippe Nougayrde Eric Oswald 《PLoS pathogens》2021,17(2)
Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells. 相似文献