全文获取类型
收费全文 | 7925篇 |
免费 | 661篇 |
国内免费 | 17篇 |
专业分类
8603篇 |
出版年
2022年 | 64篇 |
2021年 | 104篇 |
2020年 | 60篇 |
2019年 | 80篇 |
2018年 | 87篇 |
2017年 | 84篇 |
2016年 | 206篇 |
2015年 | 308篇 |
2014年 | 341篇 |
2013年 | 413篇 |
2012年 | 486篇 |
2011年 | 485篇 |
2010年 | 327篇 |
2009年 | 271篇 |
2008年 | 421篇 |
2007年 | 378篇 |
2006年 | 382篇 |
2005年 | 351篇 |
2004年 | 319篇 |
2003年 | 348篇 |
2002年 | 330篇 |
2001年 | 107篇 |
2000年 | 86篇 |
1999年 | 80篇 |
1998年 | 69篇 |
1997年 | 74篇 |
1996年 | 59篇 |
1995年 | 56篇 |
1994年 | 68篇 |
1993年 | 63篇 |
1992年 | 102篇 |
1991年 | 81篇 |
1990年 | 79篇 |
1989年 | 66篇 |
1988年 | 59篇 |
1987年 | 60篇 |
1985年 | 54篇 |
1984年 | 87篇 |
1983年 | 59篇 |
1982年 | 68篇 |
1981年 | 79篇 |
1980年 | 79篇 |
1979年 | 52篇 |
1978年 | 78篇 |
1977年 | 64篇 |
1976年 | 61篇 |
1975年 | 56篇 |
1974年 | 47篇 |
1973年 | 56篇 |
1972年 | 46篇 |
排序方式: 共有8603条查询结果,搜索用时 15 毫秒
21.
Eugene M. Rinchik Terry Magnuson Bernadette Holdener-Kenny Gavin Kelsey Albert Bianchi Claudio J. Conti Fran?ois Chartier Kathryn A. Brown Stephen D. M. Brown Josephine Peters 《Mammalian genome》1992,3(Z1):S104-S120
Chair of Committee for Mouse Chromosome 7 相似文献
22.
Gerd Wallukat Gyorgy Nemecz Tibor Farkas Hartmut Kuehn Albert Wollenberger 《Molecular and cellular biochemistry》1991,102(1):35-47
Incubation of rocker-cultured neonatal rat heart cells with 3 mM L(+)-lactate led to a sharp increase in the sensitivity of cardiomyocytes to the beta-adrenergic agonist isoprenaline, as measured by their chronotropic response. This effect was accompanied by a reduction in the arachidonic acid content of the total phospholipids. The phospholipase A2-activator melittin as well as free arachidonic acid induced this supersensitivity to the same degree. On the other hand, the L(+)-lactate-evoked supersensitivity could be blocked by the phospholipase A2 inhibitors mepacrine and n-bromophenacyl-bromide, suggesting an involvement of phospholipase A2 in the process of beta-adrenergic sensitization. The sensitizing action of arachidonic acid was blocked by the lipoxygenase inhibitors esculetin and nordihydroguaiaretic acid, but not by the cyclooxygenase inhibitor indomethacin. Supersensitivity was likewise evoked by 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), but not by 5-S-HPETE or 5-S-HETE. These findings suggest that the phospholipase A2-15-lipoxygenase pathway plays a role in the induction of beta-adrenergic supersensitivity in the cultured cardiomyocytes and point to a new physiological role of the lipoxygenase product 15-S-HETE.Abbreviations NDGA
nordihydroguaiaretic acid
- HETE
hydroeicosatetraenoic acid
- HPETE
hydroperoxyeicosatetraenoic acid 相似文献
23.
Repair of potentially lethal radiation damage in confluent and non-confluent cultures of human hybrid cells 总被引:1,自引:0,他引:1
C Sun J L Redpath M Colman E J Stanbridge 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1986,49(3):395-402
The repair of potentially lethal damage (PLDR) in a gamma-irradiated human hybrid cell line (skin fibroblast X HeLa) and its tumourigenic segregant has been studied as a function of cell density at the time of irradiation and during the postirradiation repair period. The data show that PLDR occurs in both non-confluent and confluent cultures of both cell lines. Furthermore, there is evidence that the extent of PLDR is dependent on cell density and that cell-cell contact may be an important factor in this regard. 相似文献
24.
Spectroscopic, ultrafiltration, and kinetic studies have been used to characterize interactions of reduced and oxidized triphosphopyridine nucleotides (TPNH and TPN), 2'-phosphoadenosine 5'-diphosphoribose (Rib-P2-Ado-P), and adenosine 2',5'-bisphosphate [Ado(2',5')P2] with with TPN-specific isocitrate dehydrogenase. Close similarity of the UV difference spectra and of the protein fluorescence changes accompanying the formation of the binary complexes provides evidence for the binding of these nucleotides to the same site on the enzyme. From the pH dependence of the dissociation constants for TPNH binding to TPN-specific isocitrate dehydrogenase in the absence and in the presence of Mn2+, over the pH range 5.8-7.6, it has been demonstrated that the nucleotide binds to the enzyme in its unprotonated, metal-free form. The involvement of positively charged residues, protonated over the pH range studied, has been postulated. One TPNH binding site per enzyme subunit has been measured by fluorescence and difference absorption titrations. A dramatic effect of ionic strength on binding has been demonstrated: about a 1000-fold decrease in the dissociation constant for TPNH has been observed at pH 7.6 upon decreasing ionic strength from 0.336 (Kd = 1.2 +/- 0.2 microM) to 0.036 M (Kd = 0.4 +/- 0.1 nM) in the presence and in the absence of 100 mM Na2SO4, respectively. Weak competition of sulfate ions for the nucleotide binding site has been observed (KI = 57 +/- 3 mM). The binding of TPN in the presence of 100 mM Na2SO4 at pH 7.6 is about 100-fold weaker (Kd = 110 +/- 22 microM) than the binding of the reduced coenzyme and is similarly affected by ionic strength. These results demonstrate the importance of electrostatic interactions in the binding of the coenzyme to TPN-specific isocitrate dehydrogenase. The large enhancement of protein fluorescence caused by binding of TPN and Rib-P2-Ado-P (delta Fmax = 50%) and of Ado(2',5')P2 (delta Fmax = 41%) has been ascribed to a local conformational change of the enzyme. An apparent stoichiometry of 0.5 nucleotide binding site per peptide chain was determined for TPN, Rib-P2-Ado-P, and Ado(2',5')P2 from fluorescence titrations, in contrast to one binding site per enzyme subunit determined from UV difference spectral titration and ultrafiltration experiments. Thus, the binding of one molecule of the nucleotide per dimeric enzyme molecule is responsible for the total increase in protein fluorescence, while binding to the second subunit does not cause further change.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
25.
Meiotic maturation in Xenopus oocytes: a link between the cessation of protein secretion and the polarized disappearance of Golgi apparati 总被引:10,自引:8,他引:2 下载免费PDF全文
We have studied the relationship between the timing of the late meiotic events that occur during progesterone-induced oocyte maturation, and intracellular protein transport. We have monitored the secretion of chick oviduct proteins from Xenopus laevis oocytes microinjected with polyadenylated mRNA and found that chick ovalbumin and lysozyme are not secreted during the second meiotic metaphase, in contrast to the earlier prophase stage. Maturation had no detectable effect on the glycosylation of ovalbumin, whereas it affected the glycosylation of chick ovomucoid. As maturation proceeded, the Golgi apparati disappeared in a polarized fashion, beginning in the vegetal half. This disappearance coincided temporally and spatially with that of the nuclear envelope. We speculate that Golgi apparatus disappearance and the block in secretion are causally related. 相似文献
26.
The overall internal pH of the acid-tolerant green alga, Chlorella saccharophila, was determined in the light and in the dark by the distribution of 5,5-dimethyl-2-[14C]oxazolidine-2,4-dione ([14C]DMO) or [14C]benzoic acid ([14C]BA) between the cells and the surrounding medium. [14C]DMO was used at external pH of 5.0 to 7.5 while [14C]BA was used in the range pH 3.0 to pH 5.5. Neither compound was metabolized by the algal cells and intracellular binding was minimal. The internal pH of the algae obtained with the two compounds at external pH values of 5.0 and 5.5 were in good agreement. The internal pH of C. saccharophila remained relatively constant at pH 7.3 over the external pH range of pH 5.0 to 7.5. Below pH 5.0, however, there was a gradual decrease in the internal pH to 6.4 at an external pH of 3.0. The maintenance of a constant internal pH requires energy and the downward drift of internal pH with a drop in external pH may be a mechanism to conserve energy and allow growth at acid pH. 相似文献
27.
Cleavage of human high molecular weight kininogen by factor XIa in vitro. Effect on structure and function 总被引:4,自引:0,他引:4
C F Scott L D Silver A D Purdon R W Colman 《The Journal of biological chemistry》1985,260(19):10856-10863
We have recently demonstrated that human high molecular weight kininogen (HMWK) is a pro-cofactor that is cleaved by kallikrein to yield a two-chain cofactor (HMWKa) and the nanopeptide bradykinin. This proteolysis enhances its association with an activating surface, an event necessary for expression of its cofactor activity. We now report that factor XIa is capable of hydrolyzing HMWK and releasing bradykinin in a purified system as well as cleaving and inactivating HMWK in a plasma environment during the contact-activation process. The profile of proteolysis differs from that produced by kallikrein and by factor XIIa in that the first cleavage by factor XIa yields 75- and 45-kDa polypeptides, whereas both factor XIIa and kallikrein initially produce 65- and 56-kDa species. Further proteolysis by all three enzymes eventually produces similar heavy chains (Mr = 65,000) and light chains (Mr = 45,000). However, the amount of factor XIa generated in plasma during contact activation further degrades the light chain of HMWK, eventually destroying its coagulant activity. Furthermore, in a purified system, enhancement of the degradation of HMWK coagulant activity by factor XIa was achieved when kallikrein was included in the incubation mixture, suggesting that the preferred substrate for factor XIa is the active form of HMWK (HMWKa), and not the pro-cofactor. These data suggest that factor XIa has the potential to act as a regulator of contact-activated coagulation by virtue of its ability to destroy the cofactor function of HMWK after its generation by either kallikrein, factor XIIa, or to a lesser extent, factor XIa, itself. 相似文献
28.
The effects of particle concentration and season on the filtration rates of the freshwater clamSphaerium striatinum Lamarck were assessed by measuring clearance rates of small (2.02 μm) latex beads from dilute suspensions. Filtration rates
decreased as particle concentration increased over a range of 2–64 mg 1−1, with rates decreasing in similar proportion for clams of all sizes. For a 1-mg clam, rates decreased from approximately
8.4 to 0.57 ml clam−1 h−1. Seasonal filtration rates for adult clams peaked during periods of greatest reproduction. The patterns for smaller clams
are similar, though proportional changes in filtration rates differ for various sizes of clams.
It is estimated that clams occupying 1 m2 of stream substrate removed about 3.67 gCa−1. This is equivalent to 0.0004% of the carbon that flows past them annually. Filter-feeding provided only 24% of the calculated
energy needs of the population, suggesting that another mode of feeding (e.g. deposit-feeding) may provide an important energy
source for these forms.
Funded in part by a grant-in-aid to D. J. Hornbach from Sigma-Xi, The Research Society.
Funded in part by a grant-in-aid to D. J. Hornbach from Sigma-Xi, The Research Society. 相似文献
29.
30.
The differences in conformation in solution of fluorosulfonylbenzoyl nucleosides were analyzed by fluorescence and proton nuclear magnetic resonance spectroscopy. The quantum yield of 5'-p-fluorosulfonylbenzoyl-1,N6-ethenoadenosine (5'-FSB epsilon A) in aqueous solution is low (? = 0.01) as compared to that of its parent nucleoside, ethenoadenosine (? = 0.54), and increases approximately 5-fold when measured in a series of solvents of decreasing dielectric constant. The quantum yield of 5'-p-sulfonylbenzoyl-1,N6-ethenoadenosine covalently bound to glutamate dehydrogenase and pyruvate kinase is also 0.01, suggesting that the analogue may exist in the same conformation when enzyme-bound as when free in solution. In D2O, the resonances of the purine ring protons on 5'-FSB epsilon A, 5'-p-fluorosulfonylbenzoyl adenosine (5'-FSBA), and 5'-p-fluorosulfonylbenzoyl guanosine (5'-FSBG) are shifted upfield by about 0.1-0.3 ppm relative to the corresponding protons of their parent nucleosides. The calculated difference in chemical shift (delta delta) decreases as the dielectric constant of the solvent decreases. The delta delta decreases with increasing temperature. These data indicate that 5'-FSB epsilon A, 5'-FSBA, and 5'-FSBG exist in aqueous solution in a conformation in which the purine ring is intramolecularly stacked with the benzoyl moiety. From the magnitude of change in delta delta for 5'-FSB epsilon A, 5'-FSBA, and 5'-FSBG as a function of solvent, it appears that the three analogues differ in their sensitivity to disruption of stacking. The solution conformation of these three fluorosulfonylbenzoyl nucleoside analogues may be an important determinant of their reaction with various enzymes and may explain differences among the analogues in their reaction with a single enzyme. 相似文献