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981.
C.Y. ZhangC.J. Wu W.B. ZengK.K. Huang X. LiJ.H. Feng D. WangG.H. Hua D.Q. XuQ.Y. Wen L.G. Yang 《Small Ruminant Research》2011,96(1):53-57
The polymorphism in follicle stimulating hormone beta (FSHB) subunit gene was detected by PCR-SSCP and PCR-RFLP methods in 780 does from four goat breeds including Boer, Matou, Black and Boer-Matou crossbred (BM). The associations of FSHB genotypes with litter size (LS), litter weight at birth (LWB) and gestation length (GL) as well as superovulation performances were analyzed in relatively lower-prolific Boer and higher-prolific Matou breeds. A 1514 bp linear DNA sequence of goat FSHB gene covering the complete 3 exons was cloned by four pairs of primer. A new mutation (A2645G, GenBank Accession no: S64745) locating in exon 3 causing an amino acid change from glutamine (Gln) to arginine (Arg) at residue 115 was identified, which resulted in three genotypes named AA, AB and BB. The three genotypes were detected in the four studied goat breeds. The higher-prolific Matou breed had the highest frequency of genotype AA. Association analysis showed that Boer and Matou does with AA genotype have the largest LS both in average and in parities from first to fourth (P < 0.05). Furthermore, Boer does with AA genotype had the heaviest LWB compared to other two genotypes (P < 0.05). Matou does with AA genotype have more numbers of ova harvested, large follicles and corpus lutea on ovaries after superovulation than those with BB genotype (P < 0.05). Therefore, these results suggest that the FSHB gene is a candidate gene that affects reproduction traits in goats. 相似文献
982.
983.
Hoffmann TJ Kvale MN Hesselson SE Zhan Y Aquino C Cao Y Cawley S Chung E Connell S Eshragh J Ewing M Gollub J Henderson M Hubbell E Iribarren C Kaufman J Lao RZ Lu Y Ludwig D Mathauda GK McGuire W Mei G Miles S Purdy MM Quesenberry C Ranatunga D Rowell S Sadler M Shapero MH Shen L Shenoy TR Smethurst D Van den Eeden SK Walter L Wan E Wearley R Webster T Wen CC Weng L Whitmer RA Williams A Wong SC Zau C Finn A Schaefer C Kwok PY Risch N 《Genomics》2011,98(2):79-89
The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies. 相似文献
984.
Zong S Wang Z Luo Y Zang J Wen J 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(11-12):621-626
We determined the mechanisms underlying host selection by adults of the seabuckthorn carpenterworm, Holcocerus hippophaecolus Hua, Chou, Fang et Chen. Four sea buckthorn (Hippophae rhamnoides L.) subspecies (varieties) with different degrees of resistance to H. hippophaecolus were chosen for artificial insect infection in cages. The results showed that olfactory and visual cues are very important for the selection of host plants by H. hippophaecolus, but that olfactory stimuli play a more vital role in this process. The relative abundance of branches and leaves had no effect on the likelihood that adults landed on plants from four subspecies (varieties), but did influence landing rates within the same subspecies (varieties). When considering only the most resistant sea buckthorn subspecies (varieties), the presence of luxuriant branches and leaves led to lower landing rates. These results provide a theoretical basis for the understanding of H. hippophaecolus damage to sea buckthorn and the means to implement effective measures of control. 相似文献
985.
Firooznia F Cheung AW Brinkman J Grimsby J Gubler ML Hamid R Marcopulos N Ramsey G Tan J Wen Y Sarabu R 《Bioorganic & medicinal chemistry letters》2011,21(7):1933-1936
The highly potent but modestly selective N-(2-amino-4-methoxy-benzothiazol-7-yl)-N-ethyl-acetamide derivative 2 was selected as the starting point for the design of novel selective A2B antagonists, due to its excellent potency, and good drug-like properties. A series of compounds containing nonaromatic amides or ureas of five- or six-membered rings, and also bearing an m-trifluoromethyl-phenyl group (shown to impart superior potency) was prepared and evaluated for their selectivity against the A2A and A1 receptors. This work resulted in the identification of compound 30, with excellent potency and high selectivity against both A2A and A1 receptors. 相似文献
986.
Skerlj R Bridger G Zhou Y Bourque E Langille J Di Fluri M Bogucki D Yang W Li T Wang L Nan S Baird I Metz M Darkes M Labrecque J Lau G Fricker S Huskens D Schols D 《Bioorganic & medicinal chemistry letters》2011,21(8):2450-2455
A novel series of CCR5 antagonists were identified based on the redesign of Schering C. An SAR was established based on inhibition of CCR5 (RANTES) binding and these compounds exhibited potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. 相似文献
987.
Thomas M Huang WS Wen D Zhu X Wang Y Metcalf CA Liu S Chen I Romero J Zou D Sundaramoorthi R Li F Qi J Cai L Zhou T Commodore L Xu Q Keats J Wang F Wardwell S Ning Y Snodgrass JT Broudy MI Russian K Iuliucci J Rivera VM Sawyer TK Dalgarno DC Clackson T Shakespeare WC 《Bioorganic & medicinal chemistry letters》2011,21(12):3743-3748
Ponatinib (AP24534) was previously identified as a pan-BCR-ABL inhibitor that potently inhibits the T315I gatekeeper mutant, and has advanced into clinical development for the treatment of refractory or resistant CML. In this study, we explored a novel series of five and six membered monocycles as alternate hinge-binding templates to replace the 6,5-fused imidazopyridazine core of ponatinib. Like ponatinib, these monocycles are tethered to pendant toluanilides via an ethynyl linker. Several compounds in this series displayed excellent in vitro potency against both native BCR-ABL and the T315I mutant. Notably, a subset of inhibitors exhibited desirable PK and were orally active in a mouse model of T315I-driven CML. 相似文献
988.
Huang C Moree WJ Zamani-Kord S Li BF Tucci FC Malany S Wen J Wang H Hoare SR Yang C Madan A Crowe PD Beaton G 《Bioorganic & medicinal chemistry letters》2011,21(3):947-951
Structure-activity relationship studies were conducted to reduce CYP2D6-mediated metabolism in a series of indene H1-antihistamines. Reductions in pKa via incorporation of a β-fluoro substituent or a heteroaryl moiety were shown to reduce contributions to metabolism through this pathway. Several compounds, including 8l, 8o, and 12f were identified with promising primary in vitro profiles and reduced biotransformation via CYP2D6. 相似文献
989.
Bhatt VS Guo CY Guan W Zhao G Yi W Liu ZJ Wang PG 《Protein science : a publication of the Protein Society》2011,20(5):856-866
UDP-hexose 4-epimerases play a pivotal role in lipopolysaccharide (LPS) biosynthesis and Leloir pathway. These epimerases are classified into three groups based on whether they recognize nonacetylated UDP-hexoses (Group 1), both N-acetylated and nonacetylated UDP-hexoses (Group 2) or only N-acetylated UDP-hexoses (Group 3). Although the catalysis has been investigated extensively, yet a definitive model rationalizing the substrate specificity of all the three groups on a common platform is largely lacking. In this work, we present the crystal structure of WbgU, a novel UDP-hexose 4-epimerase that belongs to the Group 3. WbgU is involved in biosynthetic pathway of the unusual glycan 2-deoxy-L-altruronic acid that is found in the LPS of the pathogen Pleisomonas shigelloides. A model that defines its substrate specificity is proposed on the basis of the active site architecture. Representatives from all the three groups are then compared to rationalize their substrate specificity. This investigation reveals that the Group 3 active site architecture is markedly different from the "conserved scaffold" of the Group 1 and the Group 2 epimerases and highlights the interactions potentially responsible for the origin of specificity of the Group 3 epimerases toward N-acetylated hexoses. This study provides a platform for further engineering of the UDP-hexose 4-epimerases, leads to a deeper understanding of the LPS biosynthesis and carbohydrate recognition by proteins. It may also have implications in development of novel antibiotics and more economic synthesis of UDP-GalNAc and downstream products such as carbohydrate based vaccines. 相似文献
990.
Wenglowsky S Ahrendt KA Buckmelter AJ Feng B Gloor SL Gradl S Grina J Hansen JD Laird ER Lunghofer P Mathieu S Moreno D Newhouse B Ren L Risom T Rudolph J Seo J Sturgis HL Voegtli WC Wen Z 《Bioorganic & medicinal chemistry letters》2011,21(18):5533-5537
Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the αC-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group. 相似文献