全文获取类型
收费全文 | 24950篇 |
免费 | 2253篇 |
国内免费 | 9篇 |
出版年
2023年 | 111篇 |
2022年 | 87篇 |
2021年 | 591篇 |
2020年 | 372篇 |
2019年 | 435篇 |
2018年 | 497篇 |
2017年 | 465篇 |
2016年 | 763篇 |
2015年 | 1244篇 |
2014年 | 1407篇 |
2013年 | 1604篇 |
2012年 | 2131篇 |
2011年 | 2164篇 |
2010年 | 1385篇 |
2009年 | 1129篇 |
2008年 | 1709篇 |
2007年 | 1601篇 |
2006年 | 1440篇 |
2005年 | 1434篇 |
2004年 | 1435篇 |
2003年 | 1230篇 |
2002年 | 1079篇 |
2001年 | 222篇 |
2000年 | 154篇 |
1999年 | 206篇 |
1998年 | 243篇 |
1997年 | 162篇 |
1996年 | 142篇 |
1995年 | 129篇 |
1994年 | 150篇 |
1993年 | 125篇 |
1992年 | 120篇 |
1991年 | 85篇 |
1990年 | 66篇 |
1989年 | 65篇 |
1988年 | 74篇 |
1987年 | 73篇 |
1986年 | 53篇 |
1985年 | 62篇 |
1984年 | 77篇 |
1983年 | 85篇 |
1982年 | 74篇 |
1981年 | 63篇 |
1980年 | 64篇 |
1979年 | 42篇 |
1978年 | 51篇 |
1977年 | 36篇 |
1976年 | 43篇 |
1975年 | 24篇 |
1974年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 638 毫秒
991.
Nelson TD Welch CJ Rosen JD Smitrovich JH Huffman MA McNamara JM Mathre DJ 《Chirality》2004,16(9):609-613
Access to a key 3-aryl-delta-lactone intermediate in enantiopure form using preparative chiral chromatography allowed expedited preparation of an important drug discovery target. A preclinical drug discovery strategy that combines rapid route discovery with effective use of preparative chiral chromatography can result in significant savings of both time and labor. 相似文献
992.
993.
Christopher?M.?Seabury James?E.?Womack Jorge?Piedrahita James?N.?DerrEmail author 《Mammalian genome》2004,15(10):828-833
The recent discovery of significant associations between bovine spongiform encephalopathy (BSE) susceptibility in German cattle and the frequency distributions of insertion/deletion (indel) polymorphisms within the bovine PRNP gene prompted an evaluation of 132 commercial U.S. artificial insemination (AI) sires from 39 breeds. Forward primer sequences from published primer sets targeting indels within the putative bovine PRNP promoter, intron 1, and the 3 UTR (untranslated region) were synthesized with unique 5 fluorescent labels and utilized to develop a rapid multiplexed PCR assay for identifying BSE-associated indels as well as facilitating polymorphism analyses and/or marker-assisted selection. Significant differences (p < 0.05 all tests) were detected between the frequencies of bovine PRNP promoter alleles for 48 healthy German cattle previously described and 132 commercial U.S. cattle sires. The frequency of the 23-bp promoter allele observed for commercial U.S. cattle sires strongly resembled that recently described for 43 BSE-affected German cattle. No significant difference (p=0.051) was detected between the distributions of promoter genotypes for healthy German cattle and our panel of commercial U.S. cattle sires. Interestingly, significant differences (p < 0.01; p < 0.02) were also noted between the frequencies and distributions of intron 1 alleles and genotypes, respectively, for BSE-affected German cattle and our panel of U.S. cattle sires. No significant allelic or genotypic differences were detected for the 14-bp 3 UTR indel for any given comparison between German cattle and commercial U.S. cattle sires. 相似文献
994.
995.
Independent genetic mechanisms mediate turgor generation and penetration peg formation during plant infection in the rice blast fungus 总被引:11,自引:0,他引:11
The first barrier to infection encountered by foliar pathogens is the host cuticle. To traverse this obstacle, many fungi produce specialized infection cells called appressoria. MST12 is essential for appressorium-mediated penetration and infectious growth by the rice pathogen Magnaporthe grisea. In this study, we have characterized in detail the penetration defects of an mst12 deletion mutant. Appressoria formed by the mst12 mutant developed normal turgor pressure and ultrastructure but failed to form penetration pegs either on cellophane membranes or on plant epidermal cells. Deletion and site-directed mutagenesis analyses indicated that both the homeodomain and zinc finger domains, but not the middle region, of MST12 are essential for appressorial penetration and plant infection. The mst12 mutant appeared to be defective in microtubule reorganization associated with penetration peg formation. In mature appressoria, the mutant lacked vertical microtubules observed in the wild type. The mst12 mutant also failed to elicit localized host defence responses, including papilla formation and autofluorescence. Our data indicate that generation of appressorium turgor pressure and formation of the penetration peg are two independent processes. MST12 may play important roles in regulating penetration peg formation and directing the physical forces exerted by the appressorium turgor in mature appressoria. 相似文献
996.
The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria 总被引:5,自引:0,他引:5
Rengarajan J Sassetti CM Naroditskaya V Sloutsky A Bloom BR Rubin EJ 《Molecular microbiology》2004,53(1):275-282
The increasing rate of multidrug-resistant tuberculosis has led to more use of second-line antibiotics such as para-aminosalicylic acid (PAS). The mode of action of PAS remains unclear, and mechanisms of resistance to this drug are undefined. We have isolated PAS-resistant transposon mutants of Mycobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant of intracellular folate levels. BCG thyA mutants have reduced thymidylate synthase activity and are resistant to known inhibitors of the folate pathway. We also find that mutations in thyA are associated with clinical PAS resistance. We have identified PAS-resistant Mycobacterium tuberculosis isolates from infected patients, which harbour mutations in thyA and show reduced activity of the encoded enzyme. Thus, PAS acts in the folate pathway, and thyA mutations probably represent a mechanism of developing resistance not only to PAS but also to other drugs that target folate metabolism. 相似文献
997.
The powerful genetics, genomics and microscopy tools available for C. elegans make it well suited to studying how epithelial cells adhere to one another and the extracellular matrix, and how the integrated, simultaneous activities of multiple cell adhesion complexes function to shape an organism. Recent studies using forward and reverse genetics have shed light on how phylogenetically conserved cell adhesion complexes, such as the cadherin/catenin complex, claudins, the Discs large complex and hemidesmosome-like attachment structures, regulate epithelial cell adhesion, providing new insights into conserved cell adhesion mechanisms in higher eukaryotes. 相似文献
998.
PURPOSE OF REVIEW: The results of a landmark clinical study comparing intensive statin therapy with conventional statin therapy, in patients with acute coronary syndromes (ACS), are reviewed. The mechanisms behind these results are analysed drawing data from vascular and cell biology. RECENT FINDINGS: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) study showed that intensive statin therapy with 80 mg of atorvastatin to achieve a low-density lipoprotein cholesterol of 62 mg/dl resulted in a 3.9% absolute and a 16% relative risk reduction in death or major cardiovascular events up to 2 years, compared to 40 mg of pravastatin, in patients with ACS. The results were especially significant as intensive statin therapy resulted in a very early benefit (<30 days) and occurred against a background of percutaneous coronary intervention (69%) for the index admission and high use of medications for secondary prevention. The PROVE IT and the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) C-reactive protein sub-study also showed that atorvastatin (80 mg) resulted in a significant reduction in markers of inflammation, whilst the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study showed that intensive statin therapy was associated with reduced progression of atherosclerosis compared with conventional doses of statins. SUMMARY: Intensive statin therapy results in a significant early reduction in adverse cardiac events in ACS patients which are sustained over 2 years. The early benefits seen are likely to result from modulation of inflammation, endothelial function and coagulation, i.e. the pleiotropic effects, whereas the greater reduction in low-density lipoprotein cholesterol results in reduced long-term events. 相似文献
999.
1000.
Rinder MR Spina RJ Peterson LR Koenig CJ Florence CR Ehsani AA 《American journal of physiology. Regulatory, integrative and comparative physiology》2004,287(2):R360-R368
To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 +/- 1.3 yr; n = 16) that exercised or to a group (age 65.3 +/- 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 +/- 12.2 vs. 11.5 +/- 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio (h/r) similarly (exercise: before 0.48 +/- 0.2, after 0.42 +/- 0.01; thiazide: before 0.47 +/- 0.04, after 0.40 +/- 0.04; P = 0.017). The reductions in systolic BP and h/r were correlated in the exercise group (r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 +/- 2.6 vs. 9.84 +/- 1.5 mU.ml(-1).min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people. 相似文献