全文获取类型
收费全文 | 6014篇 |
免费 | 357篇 |
国内免费 | 3篇 |
出版年
2021年 | 27篇 |
2019年 | 40篇 |
2018年 | 65篇 |
2017年 | 50篇 |
2016年 | 96篇 |
2015年 | 136篇 |
2014年 | 177篇 |
2013年 | 296篇 |
2012年 | 358篇 |
2011年 | 321篇 |
2010年 | 234篇 |
2009年 | 167篇 |
2008年 | 315篇 |
2007年 | 302篇 |
2006年 | 305篇 |
2005年 | 309篇 |
2004年 | 284篇 |
2003年 | 287篇 |
2002年 | 295篇 |
2001年 | 153篇 |
2000年 | 189篇 |
1999年 | 160篇 |
1998年 | 75篇 |
1997年 | 84篇 |
1996年 | 57篇 |
1995年 | 51篇 |
1994年 | 43篇 |
1993年 | 51篇 |
1992年 | 131篇 |
1991年 | 108篇 |
1990年 | 106篇 |
1989年 | 97篇 |
1988年 | 88篇 |
1987年 | 74篇 |
1986年 | 85篇 |
1985年 | 73篇 |
1984年 | 81篇 |
1983年 | 56篇 |
1982年 | 60篇 |
1981年 | 50篇 |
1980年 | 36篇 |
1979年 | 44篇 |
1978年 | 33篇 |
1977年 | 26篇 |
1976年 | 29篇 |
1975年 | 28篇 |
1974年 | 24篇 |
1973年 | 26篇 |
1970年 | 25篇 |
1967年 | 24篇 |
排序方式: 共有6374条查询结果,搜索用时 15 毫秒
41.
F Cornélis L Hashimoto J Loveridge A MacCarthy V Buckle C Julier J Bell 《Genomics》1992,13(3):820-825
The creation of a comprehensive genetic map in human has been limited by the lack of highly polymorphic markers spaced evenly throughout the human genome. We have utilized yeast artificial chromosomes (YAC) containing large human DNA inserts to help identify highly polymorphic (CA)n repeats at a chosen locus. The DNA of a YAC containing the locus was subcloned in M13 vectors, and the recombinants were screened at high stringency to detect preferentially long (CA)n repeats (n greater than 20). These repeats, which are the most likely to be highly polymorphic, were then studied to confirm both the level of polymorphism and their precise genetic location. This strategy has permitted the identification of a new, highly polymorphic CA repeat (77% heterozygosity) at the T cell receptor alpha chain (TCRA) locus on chromosome 14q. It provides a powerful marker for assessing the role of this locus in the susceptibility to autoimmune and infectious diseases. This approach should permit the development of highly polymorphic markers at any targeted locus and rapidly improve the current human genetic map. 相似文献
42.
Yoshinori Nio MD Takahiro Shiraishi Michihiko Tsubono Hideki Morimoto Chen-Chiu Tseng Kazuya Kawabata Yoshikazu Masai Manabu Fukumoto Takayoshi Tobe 《Biotherapy》1992,4(2):81-86
The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF(KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumor growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228.These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF. 相似文献
43.
Kunio Nakagawa Norio Omori Kahoko Hashimoto Tetsuya Yamamoto Takashi Tsunoda Tadao Nose 《Biotherapy》1992,4(2):109-115
Thein vitro effect of a combined treatment with lymphokine activated killer (LAK) cell and radiation therapy on rat brain tumor was examined using51Cr release assay. The tumor cell-line used in this experiment was 9L rat brain tumor derived from a Fischer 344 rat. LAK cells were obtained by culturing rat lymphocytes with recombinant human interleukin 2 for at least 3 days. The cytotoxic activity of the LAK cells was examined by51Cr release assay. Irradiation was done by exposing the microtiter plate in which the15Cr labeled 9L cells and LAK cells were cultured to a137Cs gamma cell unit. Without irradiation, there was 18% cytotoxicity in the 1:100 tumor-to-LAK cell ratio specimen after 24 hrs cocultivation. However, if 5 Gy of irradiation was given, followed by 12 hrs incubation, the cytotoxicity was enhanced significantly at the same cell ratio (30%). This enhancement effect was the most prominent when the cell ratio was 1:100 and the irradiation dose was 5 Gy. To generate the enhancement effect, an incubation time of over 8 hrs both before and after irradiation was required. The supernatant of the LAK cells showed 19.8% and 11.4% cytotoxicity with and without irradiation, respectively. This result indicates the participation of a cytotoxic factor released from LAK cells.This work is supported in part by grant from Univeristy of Tsukuba Project Research. 相似文献
44.
A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs 总被引:1,自引:0,他引:1
Kyoichi Takaori Yoshinori Nio Kazutomo Inoue Thein Tun Manaba Fukumoto Tohru Hashida Masato Yasuhara Ryohei Hori Takayoshi Tobe 《Biotherapy》1992,4(2):129-137
Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms. 相似文献
45.
Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. 总被引:2,自引:0,他引:2
Binding studies with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT), a specific serotonin1A (5-HT1A) receptor agonist, were done on the autopsied brains from control subjects and from patients with chronic schizophrenia. All the patients and controls were of the Japanese race. In the controls, representative Scatchard plots for the specific [3H]8-OH-DPAT bindings in the prefrontal cortex and hippocampus revealed a single component of high affinity binding site (Kd value = 5.7 and 5.9 nM, Bmax value = 80.1 and 101.0 fmol/mg protein, respectively). The [3H]8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin (IC50 = 6.3 x 10(-9) M) and 5-HT1A agonists (IC50 = 5.0 x 10(-9) - 2.3 x 10(-7) M), while other neurotransmitters, 5-HT2 and 5-HT3 related compounds did not inhibit the binding (IC50 greater than 10(-5) M). The bindings were decreased in the presence of 0.1mM GTP and 0.1mM GppNHp but not in the presence of 0.1mM GMP. In the prefrontal and temporal cortices of schizophrenics, there was a significant increase in the specific [3H]8-OH-DPAT binding, by 40% and 60%, respectively, with no change in the hippocampus, amygdala, cingulum, motor cortex, parietal or occipital cortex, as compared to findings in the controls. Scatchard analysis showed that this increased binding reflects changes in the number of sites but not in the affinity. The effect of 0.1mM GppNHp on the binding to prefrontal cortex was observed in both controls and schizophrenic patients. The bindings were significantly greater in the schizophrenic patients than in controls, in the presence of 0.1mM GppNHp. Our findings suggest that there are GTP-sensitive 5-HT1A sites in the human brain and that selective increases in GTP-sensitive 5-HT1A sites in the prefrontal and temporal cortices of schizophrenics relate to the pathophysiology of schizophrenia. 相似文献
46.
Formation of Nitrosylleghemoglobin in Nodules of Nitrate-Treated Cowpea and Pea Plants 总被引:1,自引:0,他引:1
The formation of nitrosylleghemoglobin (LbNO) was examined incowpea and pea nodules in relation to the inhibition of nitrogenfixation by nitrate. Leghemoglobin was of the ferrous type andwas mainly converted to LbNO in cowpea nodules when the acetylene-reducingactivity decreased to 45% of control values as a result of thesupply of nitrate. In nodules of nitrate-treated pea plants,leghemoglobin was also of the ferrous type and LbNO was a minorcomponent of leghemoglobin. The levels of LbNO isolated fromnodules corresponded to the levels of LbNO calculated from equilibriumconstants for LbNO and the concentration of nitrite in nodules.The dissociation rate constants for LbNO from both cowpea andpea were much smaller than those for LbO2 or LbCO, as is alsothe case in soybean. These results indicate that the inhibition of the functionsof leghemoglobin, due to the accumulation of LbNO, induces adecrease in nitrogen fixation in cowpea nodules, and that theinhibition of nitrogen fixation in pea nodules is not relatedto the formation of LbNO. (Received July 2, 1990; Accepted October 9, 1990) 相似文献
47.
Three germacrane-type sesquiterpenoids, (+)-germacrone-4,5-epoxide, germacrone and (+)-curdione were biotransformed by Aspergillus niger to give hydroxylated guaiane-type sesquiterpenoids together with allylic alcohols and spirolactone. 相似文献
48.
The prostacyclin (PGI2) analogues, TEI-9063 and its methyl ester, TEI-1324, have been compared with another stable analogue, iloprost, with respect to binding to the PGI2 receptor, stimulation of adenylate cyclase activity and inhibition of thrombin-induced Ca2+ mobilization in mastocytoma P-815 cells. TEI-9063 displaced the [3H]iloprost binding to the membrane fraction, the IC50 value being 3 nM, but showed very low affinity for the PGE receptor. TEI-9063 dose dependently stimulated cAMP formation in the cells and GTP-dependent adenylate cyclase activity in the membrane fraction, the EC50 value being 50 and 10 nM, respectively. Furthermore, TEI-9063 prevented the thrombin-induced increase in the intracellular Ca2+ concentration, the IC50 value being 50 nM. These IC50 and EC50 values are lower than those obtained for iloprost. On the other hand, those of TEI-1324 were about two-orders higher. Although PGI2 lost its ability to stimulate cAMP formation by preincubation for 20 min at 37 degrees C, TEI-9063 completely retained its ability after 60-min preincubation. These results demonstrate that TEI-9063 is a stable and stronger agonist for the PGI2 receptor than iloprost, and that it prevents thrombin-induced Ca2+ mobilization through stimulation of the adenylate cyclase system in mastocytoma cells. 相似文献
49.
Gyu-Chul Hwang Yoshihiro Ochiai Shugo Watabe Kanehisa Hashimoto 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1991,161(2):141-146
Summary Heavy meromyosin subfragment-1 (S1) was prepared by -chymotrypsin from myosin of carp acclimated to either 10°C or 30°C for a minimum of 5 weeks. The objective of these studies was to document thermally-induced changes in the myosin molecule and to extend previous observations. Ca2+- and K+ (EDTA)-ATPase activities of cold-acclimated carp S1 were 1.1 and 0.8 mol Pi·min-1·mg-1, respectively, and these values did not differ significantly from those of warm-acclimated carp. The inactivation rate constant (KD) of S1 from cold-acclimated carp was 32.1x10-4· s-1, compared to 13.2x10-4·s-1 for warm-acclimated carp. The maximum initial velocity of acto-S1 Mg2+-ATPase activity at pH 7.0 in 0.05 M KCl was 9.3 s-1 with cold-acclimated carp, about 3.7 times higher than that for warm-acclimated carp. However, no significant difference was observed in the apparent affinity of S1 to actin. Peptides maps of the heavy chain of S1 were different and suggested distinct isoforms for the myosins from warm- and cold-acclimated muscle.Abbreviations
ATPase
adenosine 5-triphosphatase
-
DTNB
5,5-dithiobis (2-nitrobenzoic acid)
-
DTT
dithiothreitol
-
EDTA
ethylenediaminetetraacetic acid
-
EGTA
ethyleneglycol bis (-aminoethylether)-N,N,N,N-tetraacetic acid
-
K
D
inactivation rate constant
-
K
m
apparent dissociation constant
-
P
i
inorganic -phosphate
-
PMSF
phenylmethane-sulfonyl fluoride
-
S
1
heavy meromyosin subfragment-1
-
SDS
sodium dodecyl sulfate
-
SDS-PAGE
SDS-polyacrylamide gel electrophoresis
-
TPCK
N-tosyl-l-phenylalanyl chloromethyl ketone
-
V
max
maximum initial velocity 相似文献
50.