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991.
Ono M Shitashige M Honda K Isobe T Kuwabara H Matsuzuki H Hirohashi S Yamada T 《Molecular & cellular proteomics : MCP》2006,5(7):1338-1347
We developed an integrated platform consisting of machinery and software modules that can apply vast amounts of data generated by nanoflow LC-MS to differential protein expression analyses. Unlabeled protein samples were completely digested with modified trypsin and separated by low speed (200 nl/min) one-dimensional HPLC. Mass spectra were obtained every 1 s by using the survey mode of a hybrid Q-TOF mass spectrometer and displayed in a two-dimensional plane with m/z values along the x axis, and retention time was displayed along the y axis. The time jitter of nano-LC was adjusted using newly developed software based on a dynamic programming algorithm. The comprehensiveness (60,000-160,000 peaks above the predetermined threshold detectable in 60-microg cell protein samples), reproducibility (average coefficient of variance of 0.35-0.39 and correlation coefficient of over 0.92 between duplicates), and accurate quantification with a wide dynamic range (over 10(3)) of our platform warrant its application to various types of experimental and translational proteomics. 相似文献
992.
Tanida M Niijima A Shen J Yamada S Sawai H Fukuda Y Nagai K 《Experimental biology and medicine (Maywood, N.J.)》2006,231(10):1616-1625
Previous studies have demonstrated that central injection of orexin-A affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in both anesthetized and unanesthetized rats. In the present study, we examined, using urethane-anesthetized rats, the dose-dependent effects of intravenous (iv) or intralateral cerebral ventricular (LCV) injection of various doses of orexin-A on RSNA and BP. We found that injection of a low dose of orexin-A (10 ng iv or 0.01 ng LCV) suppressed RSNA and BP significantly. Conversely, a high dose (1000 ng iv or 10 ng LCV) of orexin-A elevated both RSNA and BP significantly. Pretreatment with either iv or LCV injection of thioperamide, a histaminergic H(3)-receptor antagonist, eliminated the effects of a low dose of orexin-A on both RSNA and BP. Both iv and LCV injection of diphenhydramine, a histaminergic H(1)-receptor antagonist, abolished the effects of a high dose of orexin-A on RSNA and BP. Furthermore, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of both low and high doses of orexin-A on RSNA and BP. These findings suggest that orexin-A affects RSNA and BP in a dose-dependent manner and that the SCN and histaminergic nerve may be involved in the dose-different effects of orexin-A in rats. 相似文献
993.
Mohammad Monir Shah Yoshihiro Miyamoto Yoshihito Yamada Hirotaka Yamashita Hiroyuki Tanaka Takayuki Ezaki Hiroichi Nagai Naoki Inagaki 《Microbiology and immunology》2010,54(9):523-533
Oral supplementation of lactic acid bacteria is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis. Our previous report showed that heat‐killed Lactobacillus acidophilus strain L‐92 (L‐92) possessed anti‐allergic properties, although its physiological function in atopic dermatitis has largely remained undefined. To evaluate the anti‐allergic efficacy of L‐92, we used four experimental animal models with the major features of atopic dermatitis and compared the results to those of clinically active drugs. ICR mice were passively sensitized by anti‐dinitrophenyl mouse monoclonal IgE for passive cutaneous anaphylaxis (PCA), and BALB/c mice were actively sensitized by ovalbumin for active cutaneous anaphylaxis (ACA). Allergic reaction was induced by repeated exposure to 2,4‐dinitroflurobenzene (DNFB) and mite (Dermatophagoides farinae) fecal allergen, in BALB/c and NC/Nga mice, respectively. Orally administrated L‐92 significantly inhibited the vascular permeability increase in both PCA and ACA, and the elevation of ovalbumin‐specific IgE titer in ACA. Moreover, repeated applications of DNFB and mite fecal antigen onto the BALB/c and NC/Nga mouse ear, respectively, caused clinical symptoms similar to atopic dermatitis such as ear swelling, scratching behavior and elevation of total serum IgE levels that were also moderately suppressed by L‐92. In addition, L‐92 treated mice exhibited lower levels of mast cells, eosinophil infiltration and Th1/Th2 cytokine expression. Our results, therefore, suggest that oral administration of L‐92 might be useful for alleviating allergic symptoms. 相似文献
994.
Masanori Noguchi Tatsuyuki Kakuma Hirotsugu Uemura Yasutomo Nasu Hiromi Kumon Yasuhiko Hirao Fukuko Moriya Shigetaka Suekane Kei Matsuoka Nobukazu Komatsu Shigeki Shichijo Akira Yamada Kyogo Itoh 《Cancer immunology, immunotherapy : CII》2010,59(7):1001-1009
Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14–0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1–0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone. 相似文献
995.
Takaaki Kobayashi Mizuki Watanabe Akira Yoshida Shizuo Yamada Mika Ito Hiroshi Abe Yoshihiro Ito Mituhiro Arisawa Satoshi Shuto 《Bioorganic & medicinal chemistry》2010,18(3):1076-1082
On the basis of the previous results on a histamine H4 receptor agonist 4-methylhistamine and a cyclopropane-based conformationally restricted analog CEIC (3) with potent H3/H4 receptor antagonistic effect, 4-methylhistamine analogs 4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity (Ki = 38.7 nM) for the H3 receptor, which was more potent than a well-known H3 antagonist thioperamide. Stable tautomer and conformation of 3 and 4, which can affect the pharmacological activity, were analyzed by ab initio calculations. 相似文献
996.
997.
Katsuko Shiraya Taku Hirata Ryo Hatano Shushi Nagamori Pattama Wiriyasermkul Promsuk Jutabha Mitsunobu Matsubara Shigeaki Muto Hidekazu Tanaka Shinji Asano Naohiko Anzai Hitoshi Endou Akira Yamada Hiroyuki Sakurai Yoshikatsu Kanai 《The Journal of biological chemistry》2010,285(29):22141-22151
We identified a novel prostaglandin (PG)-specific organic anion transporter (OAT) in the OAT group of the SLC22 family. The transporter designated OAT-PG from mouse kidney exhibited Na+-independent and saturable transport of PGE2 when expressed in a proximal tubule cell line (S2). Unusual for OAT members, OAT-PG showed narrow substrate selectivity and high affinity for a specific subset of PGs, including PGE2, PGF2α, and PGD2. Similar to PGE2 receptor and PGT, a structurally distinct PG transporter, OAT-PG requires for its substrates an α-carboxyl group, with a double bond between C13 and C14 as well as a (S)-hydroxyl group at C15. Unlike the PGE2 receptor, however, the hydroxyl group at C11 in a cyclopentane ring is not essential for OAT-PG substrates. Addition of a hydroxyl group at C19 or C20 impairs the interaction with OAT-PG, whereas an ethyl group at C20 enhances the interaction, suggesting the importance of hydrophobicity around the ω-tail tip forming a “hydrophobic core” accompanied by a negative charge, which is essential for substrates of OAT members. OAT-PG-mediated transport is concentrative in nature, although OAT-PG mediates both facilitative and exchange transport. OAT-PG is kidney-specific and localized on the basolateral membrane of proximal tubules where a PG-inactivating enzyme, 15-hydroxyprostaglandin dehydrogenase, is expressed. Because of the fact that 15-keto-PGE2, the metabolite of PGE2 produced by 15-hydroxyprostaglandin dehydrogenase, is not a substrate of OAT-PG, the transport-metabolism coupling would make unidirectional PGE2 transport more efficient. By removing extracellular PGE2, OAT-PG is proposed to be involved in the local PGE2 clearance and metabolism for the inactivation of PG signals in the kidney cortex. 相似文献
998.
999.
1000.
Hiroyasu Sakai Yasuhiro Yamada Masahito Shimizu Kuniaki Saito Hisataka Moriwaki Akira Hara 《Chemico-biological interactions》2010,184(3):423-430
Colorectal cancer (CRC) is one of the most serious complications of inflammatory bowel disease. Tumor necrosis factor-α (Tnfα) is a major mediator of inflammation and there is increasing evidence that Tnfα/Tnf-receptor-1 (Tnfr1) signaling may act as an endogenous tumor promoter for colon carcinogenesis. In fact, a previous study revealed that mice lacking Tnfr1 develop significantly fewer colonic tumors in the inflammation-related CRC model. In addition, antibodies against Tnfα have been shown to inhibit the development of inflammation-related CRC. In the present study, Apc Min/+; Tnfα ?/? mice were treated with 2% dextran sodium sulfate (DSS) and the tumor development was compared with Apc Min/+; Tnfα +/+ control mice in order to investigate the role of Tnfα by itself in the inflammation-related CRC. Surprisingly, there were no detectable differences in either the severity of colonic inflammation or the expression of DSS-induced chemokines and cytokines (Ccl2, Cxcl1, Tnfβ, Il1β, Il6, and Cox-2) that relate to the colonic inflammation and tumorigenesis between these two groups. Furthermore, the genetic ablation of Tnfα did not suppress the colon tumorigenesis in comparison to the wild-type mice. Our observations suggest that intricate inflammatory responses promote the inflammation-related mouse colon tumorigenesis. 相似文献