全文获取类型
收费全文 | 15623篇 |
免费 | 1232篇 |
国内免费 | 7篇 |
出版年
2024年 | 19篇 |
2023年 | 86篇 |
2022年 | 215篇 |
2021年 | 455篇 |
2020年 | 242篇 |
2019年 | 313篇 |
2018年 | 420篇 |
2017年 | 367篇 |
2016年 | 600篇 |
2015年 | 867篇 |
2014年 | 949篇 |
2013年 | 1119篇 |
2012年 | 1435篇 |
2011年 | 1423篇 |
2010年 | 883篇 |
2009年 | 678篇 |
2008年 | 1041篇 |
2007年 | 925篇 |
2006年 | 894篇 |
2005年 | 855篇 |
2004年 | 745篇 |
2003年 | 626篇 |
2002年 | 617篇 |
2001年 | 107篇 |
2000年 | 75篇 |
1999年 | 110篇 |
1998年 | 130篇 |
1997年 | 92篇 |
1996年 | 71篇 |
1995年 | 54篇 |
1994年 | 50篇 |
1993年 | 57篇 |
1992年 | 47篇 |
1991年 | 30篇 |
1990年 | 41篇 |
1989年 | 41篇 |
1988年 | 16篇 |
1987年 | 22篇 |
1986年 | 15篇 |
1985年 | 18篇 |
1984年 | 15篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 15篇 |
1980年 | 13篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1975年 | 10篇 |
1974年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 25 毫秒
211.
Mahmood- Ul-Hassan Zahid H. Chohan Andrea Scozzafava Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):263-267
Schiff's bases were obtained from aromatic/heterocyclic sulfonamides and amino-sulfonamide derivatives, such as sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide and 5-amino-1,3,4-thiadiazole-2-sulfonamide. Metal complexes of some of these Schiff's bases, incorporating Zn(II), Co(II), Ni(II) and Cu(II) ions, were also prepared and tested as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more specifically the red blood cell isozymes I and II. The Schiff's bases behaved as medium potency CA I and CA II inhibitors, whereas their metal complexes showed a highly enhanced potency, with several low nanomolar CA II inhibitors detected. 相似文献
212.
Claudiu T. Supuran Andrea Scozzafava Marc A. Ilies Fabrizio Briganti 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):381-401
A new approach is proposed for the selective in vivo inhibition of membrane-bound versus cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes with a class of positively-charged, membrane-impermeant sulfonamides. Aromatic/heterocyclic sulfonamides acting as strong (but unselective) inhibitors of this zinc enzyme were derivatized by the attachment of trisub-stituted-pyridinium-ethylcarboxy moieties (obtained from 2, 4, 6–trisubstituted-pyrylium salts and β-alanine) to the amino, imino, hydrazino or hydroxyl groups present in their molecules. Efficient in vitro inhibition (in the nanomolar range) was observed with some of the new derivatives against three investigated CA isozymes, i.e., hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound isozyme; h = human; b = bovine isozyme). Due to their salt-like character, the new type of inhibitors reported here, unlike the classical, clinically used compounds (such as acetazolamide, methazolamide, ethoxzolamide), are unable to penetrate biological membranes, as shown by CJ vivo and in vivo perfusion experiments in rats. The level of bicarbonate excreted into the urine of the experimental animals perfused with solutions of the new and classical inhibitors suggest that: (i) when using the new type of positively-charged sulfonamides. only the membrane-bound enzyme (CA IV) was inhibited. whereas the cytosolic isozymes (CA I and II) were not affected, (ii) in the experiments in which the classical compounds (acetazolamide, bcn-zolamíde. etc.) were used. unselective inhibition of all CA isozymes (I. II and IV) occurred. 相似文献
213.
Zahid H. Chohan M.A. Farooq Andrea Scozzafava Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):1-7
Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms. 相似文献
214.
Carmen Gómez-Vaquero Alfonso Corrales Andrea Zacarías Javier Rueda-Gotor Ricardo Blanco Carlos González-Juanatey Javier Llorca Miguel A González-Gay 《Arthritis research & therapy》2013,15(4):R91
Introduction
Our objective was to determine which one of the two function charts available in Spain to calculate cardiovascular (CV) risk, Systematic COronary Risk Evaluation (SCORE) or Framingham-REgistre GIroní del COR (REGICOR), should be used in patients with rheumatoid arthritis (RA).Methods
A series of RA patients seen over a one-year period without history of CV events were assessed. SCORE, REGICOR, modified (m)SCORE and mREGICOR according to the European League Against Rheumatism (EULAR) recommendations were applied. Carotid ultrasonography (US) was performed. Carotid intima-media thickness (cIMT) > 0.90 mm and/or carotid plaques were used as the gold standard test for severe subclinical atherosclerosis and high CV risk (US+). The area under the receiver operating curves (AUC) for the predicted risk for mSCORE and mREGICOR were calculated according to the presence of severe carotid US findings (US+).Results
We included 370 patients (80% women; mean age 58.9 ± 13.7 years); 36% had disease duration of 10 years or more; rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP) were positive in 68%; and 17% had extra-articular manifestations. The EULAR multiplier factor was used in 122 (33%) of the patients. The mSCORE was 2.16 ± 2.49% and the mREGICOR 4.36 ± 3.46%. Regarding US results, 196 (53%) patients were US+. The AUC mSCORE was 0.798 (CI 95%: 0.752 to 0.844) and AUC mREGICOR 0.741 (95% CI; 0.691 to 0.792). However, mSCORE and mREGICOR failed to identify 88% and 91% of US+ patients. More than 50% of patients with mSCORE ≥1% or mREGICOR >1% were US+.Conclusions
Neither of these two function charts was useful in estimating CV risk in Spanish RA patients. 相似文献215.
Isabella Panfoli Laura Santucci Maurizio Bruschi Andrea Petretto Daniela Calzia Luca A. Ramenghi 《Expert review of proteomics》2013,10(10):801-808
ABSTRACTIntroduction: Shed by most cells, in response to a myriad of stimuli, extracellular vesicles (EVs) carry proteins, lipids, and various nucleic acids. EVs encompass diverse subpopulations differing for biogenesis and content. Among these, microvesicles (MVs) derived from plasma membrane, are key regulators of physiopathological cellular processes including cancer, inflammation and infection. This review is unique in that it focuses specifically on the MVs as a mediator of information transfer. In fact, few proteomic studies have rigorously distinguished MVs from exosomes.Areas covered: Aim of this review is to discuss the proteomic analyses of the MVs. Many studies have examined mixed populations containing both exosomes and MVs. We discuss MVs’ role in cell-specific interactions. We also show their emerging roles in therapy and diagnosis.Expert commentary: We see MVs as therapeutic tools for potential use in precision medicine. They may also have potential for allowing the identification of new biomarkers. MVs represent an invaluable tool for studying the cell of origin, which they closely represent, but it is critical to build a repository with data from MVs to deepen our understanding of their molecular repertoire and biological functions. 相似文献
216.
Alica Chocholova Andrea Soltysova Gabriel Minarik Iveta Cierna Sabina Sufliarska Beata Mladosievicova 《Nucleosides, nucleotides & nucleic acids》2013,32(5):239-246
Thiopurine methyltransferase (TPMT) is a key component in thiopurine metabolism. There is an insufficient evidence about the distribution of the genotype frequencies of TPMT variants and frequencies of TPMT alleles associated with intermediate and deficient activity in a healthy Slovak population and pediatric patients with inflammatory bowel disease (IBD). TPMT variant alleles (*1,*2, *3A, *3B, and *3C) were determined in 114 children treated for IBD and in 281 healthy volunteers. Mutant alleles were present in 9/114 (7.89%) in the IBD patients and in 23/281 (8.19%) of probands. The distribution of the most frequent variants of TPMT gene was similar in a healthy population and patients with IBD. 相似文献
217.
218.
Sophie Herszterg Andrea Leibfried Floris Bosveld Charlotte Martin Yohanns Bellaiche 《Developmental cell》2013,24(3):256-270
Highlights? During cytokinesis, neighboring cells accumulate MyoII at the edges of the furrow ? MyoII nonautonomously sets the initial geometry of the daughter cell interface ? Neighboring membranes impede adherens junction (AJ) formation until a midbody forms ? Arp2/3-dependent actin accumulation in the dividing cell maintains AJ geometry 相似文献
219.
Karine Lambou Andrea Pennati Isabel Valsecchi Rui Tada Stephen Sherman Hajime Sato Remi Beau Giovanni Gadda Jean-Paul Latgé 《Eukaryotic cell》2013,12(6):853-863
The choline oxidase (CHOA) and betaine aldehyde dehydrogenase (BADH) genes identified in Aspergillus fumigatus are present as a cluster specific for fungal genomes. Biochemical and molecular analyses of this cluster showed that it has very specific biochemical and functional features that make it unique and different from its plant and bacterial homologs. A. fumigatus ChoAp catalyzed the oxidation of choline to glycine betaine with betaine aldehyde as an intermediate and reduced molecular oxygen to hydrogen peroxide using FAD as a cofactor. A. fumigatus Badhp oxidized betaine aldehyde to glycine betaine with reduction of NAD+ to NADH. Analysis of the AfchoAΔ::HPH and AfbadAΔ::HPH single mutants and the AfchoAΔAfbadAΔ::HPH double mutant showed that AfChoAp is essential for the use of choline as the sole nitrogen, carbon, or carbon and nitrogen source during the germination process. AfChoAp and AfBadAp were localized in the cytosol of germinating conidia and mycelia but were absent from resting conidia. Characterization of the mutant phenotypes showed that glycine betaine in A. fumigatus functions exclusively as a metabolic intermediate in the catabolism of choline and not as a stress protectant. This study in A. fumigatus is the first molecular, cellular, and biochemical characterization of the glycine betaine biosynthetic pathway in the fungal kingdom. 相似文献
220.