全文获取类型
收费全文 | 5191篇 |
免费 | 292篇 |
国内免费 | 1篇 |
出版年
2022年 | 16篇 |
2021年 | 56篇 |
2020年 | 25篇 |
2019年 | 34篇 |
2018年 | 51篇 |
2017年 | 50篇 |
2016年 | 84篇 |
2015年 | 158篇 |
2014年 | 175篇 |
2013年 | 286篇 |
2012年 | 258篇 |
2011年 | 279篇 |
2010年 | 195篇 |
2009年 | 198篇 |
2008年 | 278篇 |
2007年 | 288篇 |
2006年 | 299篇 |
2005年 | 304篇 |
2004年 | 332篇 |
2003年 | 295篇 |
2002年 | 267篇 |
2001年 | 124篇 |
2000年 | 122篇 |
1999年 | 137篇 |
1998年 | 68篇 |
1997年 | 61篇 |
1996年 | 48篇 |
1995年 | 51篇 |
1994年 | 52篇 |
1993年 | 42篇 |
1992年 | 86篇 |
1991年 | 60篇 |
1990年 | 75篇 |
1989年 | 57篇 |
1988年 | 59篇 |
1987年 | 45篇 |
1986年 | 52篇 |
1985年 | 61篇 |
1984年 | 45篇 |
1983年 | 34篇 |
1982年 | 26篇 |
1981年 | 35篇 |
1979年 | 27篇 |
1978年 | 32篇 |
1977年 | 20篇 |
1976年 | 20篇 |
1975年 | 18篇 |
1973年 | 18篇 |
1972年 | 13篇 |
1970年 | 12篇 |
排序方式: 共有5484条查询结果,搜索用时 15 毫秒
991.
Bengea S Araki Y Ito O Igarashi J Sagami I Shimizu T 《Journal of inorganic biochemistry》2004,98(7):1210-1216
The effects of substrates, inhibitors and tetrahydrobiopterin (H4B) on CO rebinding to the isolated heme-bound oxygenase domain (nNOSox) of neuronal nitric oxide synthase were examined by laser flash photolysis. The rate constant of CO recombination with substrate and inhibitor-free nNOSox in the absence of H4B was 1.0 x 10(6) M(-1) s(-1). The addition of H4B led to a marked decrease in the rate to 0.59 x 10(6) M(-1) s(-1). Interestingly, the substrates, L-Arg and N-hydroxy-L-Arg (NHA), altered CO binding behavior in that the binding rate was modified to CO concentration-independent, both with and without H4B. In the absence of H4B, agmatine, NG-monomethyl-L-Arg (NMMA) and NG-nitro-L-Arg methyl ester (NAME) decreased the CO concentration-dependent rate constants of rebinding by half (0.43 x 10(6) M(-1) s(-1) for the NMMA-bound complex), whereas N6-(l-iminoethyl)-L-Lys (NIL) and 7-nitro-1H-indazole (7-NI) increased the rate constants by more than 70% (up to 2.1 x 10(6) M(-1) s(-1) for the NIL-bound complex). In the presence of H4B, the binding rate was independent of CO concentration for the agmatine-bound complex. The differential effects of the inhibitors on the CO concentration-dependent rate constants were significantly diminished for the H4B-bound system. Interestingly, these variable effects of inhibitors on the CO binding rate were more pronounced in the absence of H4B. Accordingly, we suggest that H4B significantly influences CO binding by altering the CO access channel, and further reduces the divergent effects of different inhibitors. 相似文献
992.
993.
Ogino Y Ohtake N Kobayashi K Kimura T Fujikawa T Hasegawa T Noguchi K Mase T 《Bioorganic & medicinal chemistry letters》2003,13(13):2167-2172
Optimization of the amine part of our original muscarinic M(3) receptor antagonist 1 was performed to identify M(3) receptor antagonists that are superior to 1. Compounds carrying a variety of diamine moieties without hydrophobic substituent on the nitrogen atom were screened against the binding affinity for the M(3) receptor and the selectivity for M(3) over the M(1) and M(2) receptors. This process led to a 4-aminopiperidinamide (2l) with a K(i) value of 5.1 nM and with a selectivity of the M(3) receptor that was 46-fold greater than that of the M(2) receptor. Further derivatization of 2l by inserting a spacer group or by incorporating alkyl group(s) into the amine part resulted in the identification of an 4-(aminoethyl)piperidinamide 2l-b with a K(i) value of 3.7 nM for the M(3) receptor and a selectivity for the M(3) receptor that was 170-fold greater than that of the M(2) receptor. 相似文献
994.
The thermophilic filamentous phototroph Chloroflexus aggregans was able to form a bacterial mat-like dense cell aggregate rapidly. The aggregate formation, which was observed in growing cells in a liquid medium in a bottle, occurred every time within 20-30 min after the cells were dispersed by shaking. The aggregation depended on the energy supplied by photosynthesis or respiration. Cells aggregated most rapidly under temperature and pH conditions that support maximum growth. The aggregation was also accelerated by the addition of 3-isobutyl-1-methylxanthine that inhibits cyclic 3',5'-AMP phosphodiesterase. Microscopic observation revealed that the bacterium has a fast gliding mobility (1-3 microm s(-1)). The distinctive cell aggregation of C. aggregans was due to this rapid gliding movement. 相似文献
995.
Kondoh M Kasai T Shimada M Kashiwayanagi M Yokosawa H 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2003,134(3):417-423
The transient receptor potential (TRP) ion channels are thought to be involved in the entry of calcium ion into cells. In this study, we isolated a cDNA clone, HrTRPV, that shows high homology to Caenorhabditis elegans OSM-9, a TRPV subfamily member of the TRP family, from a Halocynthia roretzi fertilized egg cDNA library. We analyzed its properties using HrTRPV-transfected cells. Upon reduction of extracellular osmolarity, the intracellular calcium concentration was found to increase in HrTRPV-transfected cells. This increase in intracellular calcium concentration was dependent on the presence of extracellular calcium ion and was inhibited by treatment with gadolinium ion, a stretch-activated calcium channel blocker. Thus, these results indicate that ascidian egg HrTRPV is an osmotically sensitive TRP channel. 相似文献
996.
997.
Saito N Sasaki T Furuse M Arakawa K Shimada K 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2001,128(1):147-153
In birds, arginine vasotocin (AVT) and mesotocin (MT) are the neurohypophyseal hormones. AVT is known to be an avian antidiuretic hormone and is released from the neurohypophysis by dehydration or hyperosmotic stimulation. The purpose of this study was to determine whether the mechanism of AVT synthesis is related to the mechanism of hormone release from the neurohypophysis. Four-day-old chicks received an AVT antisense oligodeoxynucleotide (ODN) injection into the cerebral ventricle (icv). Following antisense administration, the chicks received hypertonic saline stimulation. Plasma levels of AVT and MT were measured by radioimmunoassays. In control birds, a hypertonic saline injection resulted in the increase of plasma AVT level. The administration of a high dose (50 microg) of antisense ODN inhibited the increase of plasma AVT level induced by the hypertonic saline stimulation. Plasma levels of MT did not change with the administration of hypertonic saline or antisense ODN. These results suggest that the mechanisms that regulate the secretion of AVT from the neurohypophysis may be coupled to the mechanisms that regulate the synthesis of AVT. 相似文献
998.
Akemi Shimada Satoshi Wada Kouji Inoue Hisashi Ideno Taichi Kamiunten Koichiro Komatsu Akira Kudo Yoshiki Nakamura Tetsuji Sato Kazuhisa Nakashima Akira Nifuji 《Histochemistry and cell biology》2014,142(2):205-215
Development of regenerative therapies for damaged tendons remains a great challenge, largely because of lack of information regarding the mechanisms responsible for differentiation of tenocytes. Mouse tenocytes have not been fully characterized owing to the absence of efficient and reproducible methods for their in vitro expansion without losing phenotypic features. The objective of the study was to establish an improved and reliable method for stable primary culture of mouse tenocytes by using collagen gel. Achilles and tail tendon tissues were harvested and embedded in collagen gel. After 10 days of continuous culture, the gel was digested and cells were passaged on tissue culture-treated plastic dishes. Mouse tenocytes cultured in collagen gel exhibited significantly shorter doubling time and higher numbers of proliferation when maintained on the plastic dishes compared with those cultured without using gel. Transmission electron microscopic analyses showed that cultured tenocytes retained some morphological features of tenocytes in tendon tissues, such as cell–cell junctional complex formation, well-developed rough endoplasmic reticulum, and mitochondria in their cytoplasm. mRNA expression of tenocyte markers (tenomodulin, type I collagen, periostin, and scleraxis) was higher in cells cultured in collagen gel than in those cultured in the absence of gel. Our results show that tenocytes cultured using the collagen gel method express typical lineage markers and exhibit improved growth characteristics, thus providing a stable platform for studying molecular mechanisms that control their differentiation. 相似文献
999.
Takuji Ichino Kentaro Fuji Haruko Ueda Hideyuki Takahashi Yasuko Koumoto Junpei Takagi Kentaro Tamura Ryosuke Sasaki Koh Aoki Tomoo Shimada Ikuko Hara‐Nishimura 《The Plant journal : for cell and molecular biology》2014,80(3):410-423
Flavonoids are the most important pigments for the coloration of flowers and seeds. In plant cells, flavonoids are synthesized by a multi‐enzyme complex located on the cytosolic surface of the endoplasmic reticulum, and they accumulate in vacuoles. Two non‐exclusive pathways have been proposed to mediate flavonoid transport to vacuoles: the membrane transporter‐mediated pathway and the vesicle trafficking‐mediated pathway. No molecules involved in the vesicle trafficking‐mediated pathway have been identified, however. Here, we show that a membrane trafficking factor, GFS9, has a role in flavonoid accumulation in the vacuole. We screened a library of Arabidopsis thaliana mutants with defects in vesicle trafficking, and isolated the gfs9 mutant with abnormal pale tan‐colored seeds caused by low flavonoid accumulation levels. gfs9 is allelic to the unidentified transparent testa mutant tt9. The responsible gene for these phenotypes encodes a previously uncharacterized protein containing a region that is conserved among eukaryotes. GFS9 is a peripheral membrane protein localized at the Golgi apparatus. GFS9 deficiency causes several membrane trafficking defects, including the mis‐sorting of vacuolar proteins, vacuole fragmentation, the aggregation of enlarged vesicles, and the proliferation of autophagosome‐like structures. These results suggest that GFS9 is required for vacuolar development through membrane fusion at vacuoles. Our findings introduce a concept that plants use GFS9‐mediated membrane trafficking machinery for delivery of not only proteins but also phytochemicals, such as flavonoids, to vacuoles. 相似文献
1000.
Yousuke Kouno Makoto Anraku Keishi Yamasaki Yoshiro Okayama Daisuke Iohara Yu Ishima Toru Maruyama Ulrich Kragh-Hansen Fumitoshi Hirayama Masaki Otagiri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014