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991.
The pollen morphology of 37 species of Trichosanthes was examined, using light microscopy, and scanning and transmission electron microscopy. On the basis of the diverse exine ornamentation it is possible to distinguish five pollen types. With aperture characters, two of them can be subdivided into subtypes. Two types can be characterised with ultrastructural features as well. It appeared that several of the types (alt. subtypes) correspond very well to existing macromorphological groupings. The most deviating type, including only the monotypic section Trichosanthes (T. cucumerina), shows verrucate ornamentation, a thick granular infratectum and a thin, indistinctly delimited nexine. It is similar to that of the Madagascan genus Tricyclandra. 相似文献
992.
Relatively small, microreticulate-gemmate acalymmate tetrads with coarsely verrucate inner nexine surfaces are described for the monotypic genus Borneosicyos. Tetrads represent a new pollen type in Old World Cucurbitaceae, while microreticulate-gemmate ornamentation and a verrucate inner nexine surface were unknown so far in the entire family. 相似文献
993.
Raymond van der Ham Gijs Grob Wilbert Hetterscheid Wim Star Bertie Joan van Heuven 《Grana》2013,52(4):252-265
A strict consensus tree based on chloroplast and nuclear sequences (rbcL, matK, trnL, FLint2) from 46 Amorphophallus species, two Pseudodracontium species and six outgroups is used to develop a hypothesis for the evolution of ornamentation and ectexine ultrastructure in the pollen of Amorphophallus. There are four main clades: an exclusively African, largely psilate clade (‘African clade’), an Asian, largely psilate clade (‘Asian psilate clade’) and an Asian, largely striate clade consisting of a mainly continental SE Asian clade (‘continental SE Asian striate clade’) and one centred in Malesia (‘Malesian striate clade’). Ultrastructure provides a valuable contribution towards understanding pollen ornamentation in Amorphophallus. Pollen with a thin psilate ectexine without dark granules might be plesiomorphic in Amorphophallus. Then the diverse striate type would be derived. Within both striate clades, reversals to the psilate type occur. Striate pollen with psilate caps, which is nested in the continental SE Asian striate clade, is a synapomorphy of Pseudodracontium. The fossulate type is also diverse, and its distribution in the tree indicates a polyphyletic origin. Areolate, echinate and verrucate ornamentation, occur in single species in the tree, but are found also in species not included in the molecular analysis. All three are heterogeneous and probably polyphyletic too. Reticulate, scabrate and striate/scabrate ornamentation are autapomorphies, of which the reticulate type and the striate/scabrate type may derive from psilate and striate ornamentation, respectively. Of the four main clades, the Asian psilate and African clade seem to be basal, while both striate clades might have evolved from the Asian psilate clade via a species like A. rhizomatosus. Dark granules evolved more than once, which might explain their diverse size, shape and distribution. 相似文献
994.
Jason D. Downey Sam A. Saleh Thomas M. Bridges Ryan D. Morrison J. Scott Daniels Craig W. Lindsley Richard M. Breyer 《Bioorganic & medicinal chemistry letters》2013,23(1):37-41
Recent preclinical studies demonstrate a role for the prostaglandin E2 (PGE2) subtype 1 (EP1) receptor in mediating, at least in part, the pathophysiology of hypertension and diabetes mellitus. A series of amide and N-acylsulfonamide analogs of a previously described picolinic acid-based human EP1 receptor antagonist (7) were prepared. Each analog had improved selectivity at the mouse EP1 receptor over the mouse thromboxane receptor (TP). A subset of analogs gained affinity for the mouse PGE2 subtype 3 (EP3) receptor, another potential therapeutic target. One analog (17) possessed equal selectivity for EP1 and EP3, displayed a sufficient in vivo residence time in mice, and lacked the potential for acyl glucuronide formation common to compound 7. Treatment of mice with 17 significantly attenuated the vasopressor activity resulting from an acute infusion of EP1 and EP3 receptor agonists. Compound 17 represents a potentially novel therapeutic in the treatment of hypertension and diabetes mellitus. 相似文献
995.
James S. Scott Katy J. Brocklehurst Hayley S. Brown David S. Clarke Helen Coe Sam D. Groombridge David Laber Philip A. MacFaul Darren McKerrecher Paul Schofield 《Bioorganic & medicinal chemistry letters》2013,23(11):3175-3179
A series of conformationally restricted GPR119 agonists were prepared based around a 3,8-diazabicyclo[3.2.1]octane scaffold. Examples were found to have markedly different pharmacology in mouse and human despite similar levels of binding to the receptor. This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors. 相似文献
996.
Zhinxin Zhao Roberto Gambari Kenneth Ka-Ho Lee Stanton Hon-Lung Kok Raymond Siu-Ming Wong Fung-Yi Lau Johnny Cheuk-On Tang Kim-Hung Lam Chor-Hing Cheng Desmond Kwok Po Hau Chung-Hin Chui Wai-Yeung Wong Wai-Kwok Wong 《Bioorganic & medicinal chemistry letters》2013,23(8):2373-2376
We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified. 相似文献
997.
David C. Kombo Terry A. Hauser Vladimir P. Grinevich Matthew S. Melvin Jon-Paul Strachan Serguei S. Sidach Joseph Chewning Nikolai Fedorov Kartik Tallapragada Scott R. Breining Craig H. Miller 《Bioorganic & medicinal chemistry letters》2013,23(5):1450-1455
We have carried out a pharmacological evaluation of arylmethylene quinuclidine derivatives interactions with human α3β4 nAChRs subtype, using cell-based receptor binding, calcium-influx, electrophysiological patch-clamp assays and molecular modeling techniques. We have found that the compounds bind competitively to the α3β4 receptor with micromolar affinities and some of the compounds behave as non-competitive antagonists (compounds 1, 2 and 3), displaying submicromolar IC50 values. These evidences suggest a mixed mode of action for these compounds, having interactions at the orthosteric site and more pronounced interactions at an allosteric site to block agonist effects. One of the compounds, 1-benzyl-3-(diphenylmethylene)-1-azoniabicyclo[2.2.2]octane chloride (compound 3), exhibited poorly reversible use-dependent block of α3β4 channels. We also found that removal of a phenyl group from compound 1 confers a partial agonism to the derived analog (compound 6). Introducing a hydrogen-bond acceptor into the 3-benzylidene quinuclidine derivative (compound 7) increases agonism potency at the α3β4 receptor subtype. Docking into the orthosteric binding site of a α3β4 protein structure derived by comparative modeling accurately predicted the experimentally-observed trend in binding affinity. Results supported the notion that binding requires a hydrogen bond formation between the ligand basic nitrogen and the backbone carbonyl oxygen atom of the conserved Trp-149. 相似文献
998.
Peter W. Glunz Xiaojun Zhang Yan Zou Indawati Delucca Alexandra H. Nirschl Xuhong Cheng Carolyn A. Weigelt Daniel L. Cheney Anzhi Wei Rushith Anumula Joseph M. Luettgen Alan R. Rendina Mark Harpel Gang Luo Robert Knabb Pancras C. Wong Ruth R. Wexler E. Scott Priestley 《Bioorganic & medicinal chemistry letters》2013,23(18):5244-5248
Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P′ binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype. 相似文献
999.
Lavanya Bondada Ramu Rondla Ugo Pradere Peng Liu Chengwei Li Drew Bobeck Tamara McBrayer Philip Tharnish Jerome Courcambeck Philippe Halfon Tony Whitaker Franck Amblard Steven J. Coats Raymond F. Schinazi 《Bioorganic & medicinal chemistry letters》2013,23(23):6325-6330
Herein, we report the synthesis and structure–activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC50 = 0.8 μM). 相似文献
1000.
Horrick Sharma Tino W. Sanchez Nouri Neamati Mervi Detorio Raymond F. Schinazi Xiaolin Cheng John K. Buolamwini 《Bioorganic & medicinal chemistry letters》2013,23(22):6146-6151
In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound of the series, inhibiting both 3′-end processing (3′-P) and strand transfer (ST) with IC50 values of 5 and 1.3 μM, respectively. Docking studies revealed two predominant binding modes that were distinct from the binding modes of raltegravir and elvitegravir, and suggest a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact significantly with some of the key amino acids (Q148 and N155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV-1 IN inhibitors. 相似文献